Cucullanus bagre Petter, 1974 (Cucullanidae) is redescribed based on the examination of newly collected material and the revaluation of type specimens, using light and for the first time scanning electron microscopy. Parasite specimens were collected from the intestine of the coco sea catfish Bagrebagre (Linnaeus) (Ariidae) off the South Atlantic coast, State of Rio de Janeiro, Brazil. Detailed morphological analysis revealed the presence of an unpaired papilla just anterior to the cloacal protrusion in male, that was overlooked in the original description. Descriptions of the adult female and eggs are provided for the first time; these gravid specimens have the general morphometry quite similar to that of juveniles. Additionally, detailed description and illustration of sclerotized plates present on the oesophastome is provided. The far posterior location of the excretory pore with thick-walled excretory duct, the conspicuous protrusions present on both anal and cloacal regions and the number and arrangement of caudal papillae in males are considered to be important diagnostic features for C. bagre. All the specimens from type material were together in one vial and not separated in two vials as stated in the original description, making it impossible to determine which is the holotype, allotype or paratypes. This is the first report of C. bagre in Brazil, which expands its geographical distribution to South Atlantic waters.

In spite of the abundance and commercial importance of these two species, there is little published weight-length data for the gafftopsail catfish ...Bagre marinus) and hardhead catfish (Ariopsis felis). For this study 84 catfish were caught (hook and line) from the Calcasieu Estuary in Southwest

... depending on the type of muscular dystrophy. Duchenne muscular dystrophy About half of people with muscular dystrophy have ... muscles Muscle pain and stiffness Learning disabilities Becker muscular dystrophy Signs and symptoms are similar to those of ...

... Devices The Search for a Cure en español Distrofia muscular About MD Muscular dystrophy (MD) is a ... muscles and cause different degrees of muscle weakness. Duchenne muscular dystrophy is the most common and the ...

The department of Antioquia in Columbia is the main producer of gold in Columbia. In the gold-producing regions the population is exposed to high levels of mercury used in the processes of extraction and purification. Studies done in Columbia on neurotoxicity underline the hazards of mercury from the environmental and occupational-health point of view, but the effect of long-term exposure on cognitive function has not been studied. To determine whether the miners of El Bagre (Antioquia, Columbia) have neuropsychological and/or behavior disorders as a result of occupational exposure to toxic mercury vapor. The sample was made up of 22 right-handed men, residents of El Bagre, aged between 20 and 45 years old who had been exposed to mercury vapor for at least three years. The control group consisted of 22 men who lived in the non-mining regions of the department and had not been exposed to mercury, paired with the cases considered for age and educational status. Neuropsychological assessment, a medical examination and behavioral performance tests were applied to all the men (in both groups). In the study group alterations were seen and classified as: intellectual damage (mainly alteration of executive function and constructional praxis); emotional changes (symptoms of depression and anxiety) and neurological changes (amnesia, insomnia and tremor of the tongue). No changes were found in the control group. Exposure to mercury causes specific neuropsychological and behavior disorders in the absence of clinically detectable physical or physiological damage.

Muscular dystrophy (MD) is a group of more than 30 inherited diseases. They all cause muscle weakness and ... ability to walk. There is no cure for muscular dystrophy. Treatments can help with the symptoms and prevent ...

... this page: //medlineplus.gov/ency/article/001190.htm Muscular dystrophy To use the sharing features on this page, please enable JavaScript. Muscular dystrophy is a group of inherited disorders that cause ...

... It Like for Teens With MD? en español Distrofia muscular Aside from seeing the telethon on Labor ... which weakens different muscle groups in various ways: Duchenne (pronounced: due-SHEN) muscular dystrophy (DMD) , the most ...

... affects about 1 out of every 3,500 boys. (Girls can carry the gene that causes the disease, ... and heart problems. Limb-girdle muscular dystrophy affects boys and girls equally. Symptoms usually start when kids are between ...

... be affected. Limb-girdle muscular dystrophy (LGMD) affects boys and girls equally, weakening muscles in the shoulders and upper ... weakness and poor muscle tone. Occurring in both girls and boys, it can have different symptoms. It varies in ...

Monitoring turbidity and Surface Suspended Sediment Concentration (SSSC) of inland waters is essential to address several important issues: erosion, sediment transport and deposition throughout watersheds, reservoir siltation, water pollution, human health risks, etc. This is especially important in regions with limited conventional monitoring capacities such as West Africa. In this study, we explore the use of Moderate Resolution Imaging Spectroradiometer data (MODIS, MOD09Q1 and MYD09Q1 products, red (R) and near infrared (NIR) bands) to monitor turbidity and SSSC for the Bagre Reservoir in Burkina Faso. High values ​​of these parameters associated with high spatial and temporal variability potentially challenge the methodologies developed so far for less turbid waters. Field measurements (turbidity, SSSC, radiometry) are used to evaluate different radiometric indices. The NIR/R ratio is found to be the most suited to retrieve SSSC and turbidity for both in-situ spectoradiometer measurements and satellite reflectance from MODIS. The spatio temporal variability of MODIS NIR/R together with rainfall estimated by the Tropical Rainforest Measuring Mission (TRMM) and altimetry data from Jason-2 is analyzed over the Bagre Reservoir for the 2000-2015 period. It is found that rain events of the early rainy season (February-March) through mid-rainy season (August) are decisive in triggering turbidity increase. Sediment transport is observed in the reservoir from upstream to downstream between June and September. Furthermore, a significant increase of 19% in turbidity values is observed between 2000 and 2015, mainly for the July to December period. It is especially well marked for August, with the central and downstream areas showing the largest increase. The most probable hypothesis to explain this evolution is a change in land use, and particularly an increase in the amount of bare soils, which enhances particle transport by runoff.

... Disorders 2003 News Release Fischbeck Group Learning About Spinal Muscular Atrophy What is spinal muscular atrophy? What are the ... Additional Resources for Spinal Muscular Atrophy What is spinal muscular atrophy? Spinal muscular atrophy is a group of inherited ...

... here Home » Disorders » Patient & Caregiver Education » Fact Sheets Spinal Muscular Atrophy Fact Sheet What is spinal muscular atrophy? What ... Where can I get more information? What is spinal muscular atrophy? Spinal muscular atrophy (SMA) is one of several ...

Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3,500 live male births in the world. The diagnosis should be confirmed by genetic testing to identify the mutation in the DMD gene or muscle biopsy and immunostaining to demonstrate the absence of dystrophin. Although up to now continues to be an incurable disease, this does not mean it has no treatment. Treatment should be multidisciplinary, looking for the functionality of the patient and avoiding or correcting complications, mainly cardio-respiratory and skeletal. Many proposals have been evaluated and implemented with the aim of improving the quality of life for these patients. The long-term steroids have shown significant benefits, such as prolonging ambulation, reduce the need for spinal surgery, improve cardiorespiratory function and increase survival and the quality of life. This document presents the recommendations based on the experience of the working group and experts worldwide on the diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy.

This definition of flexibility and muscular strength also explores their roles in overall physical fitness and focuses on how increased flexibility and muscular strength can help decrease or eliminate lower back pain. (CB)

This definition of flexibility and muscular strength also explores their roles in overall physical fitness and focuses on how increased flexibility and muscular strength can help decrease or eliminate lower back pain. (CB)

... this page: //medlineplus.gov/ency/article/000996.htm Spinal muscular atrophy To use the sharing features on this page, please enable JavaScript. Spinal muscular atrophy is a group of disorders of the motor ...

... MD Living With MD en español Qué significa distrofia muscular What Is Muscular Dystrophy? Muscular dystrophy (say: MUS- ... blood test if a kid has Becker or Duchenne MD. Or the doctor might take a small piece of the muscle and look at it under a microscope to ...

Advances in molecular genetics on lasts 15 years had modified profoundly our knowledge about muscular dystrophies. The pathogenia, caused by defectives proteins which disrupt dystrophin-associated-protein complex in most of the dystrophies, has generate a new classification based in protein and genomic defects. In this review, clinical, genetic, diagnostic and therapeutic aspects of the main muscular dystrophies are described. Limb girdle muscular dystrophies with Duchenne-like phenotype (sarcoglycanopathies), are identified by immunohistochemistry, as X-linked Emery-Dreifuss muscular dystrophy (emerin deficit), and classical congenital muscular dystrophy (merosine depletion). The others limb girdle muscular dystrophies, an heterogeneous phenotypical group, are detected by Western blot (mainly calpainopathies), or inmunohistochemistry in muscle (caveolinopathies) and blood (dysferlinopathies). Congenital muscular dystrophies with brain malformations: Fukuyama, muscle-eye-brain, and Walker-Warburg syndrome; and fukutin-related protein dystrophy, only may be differentiated by genetic analysis. All them shows alpha-dystroglican depletion. Autosomal dominant Emery-Dreifuss muscular dystrophy and facioscapulohumeral dystrophy are exclusively identified by DNA study. Finally, Duchenne/Becker muscular dystrophies are diagnosed by immunohistochemistry, Western blot and/or DNA analysis. Treatment of muscular dystrophies is based in physiotherapy, ventilatory support, surgery and drugs (mainly steroids, effective in Duchenne/Becker muscular dystrophies). Genic and cellular therapy are yet on experimental field, and are matter of the future. Now, accurate diagnosis is important for therapeutic management, prognosis and genetic counseling.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the SMN1 (survival motor neuron) gene. It is classified by age of onset and maximal motor milestones achieved in type I, II, and III (severe, intermediate, and mild form, respectively). Of 369 unrelated SMA patients who were investigated for homozygous deletions in the SMN1 gene, 18 patients (4.8%) revealed at least one copy of exon 7. A 4-bp deletion in exon 3 (c.399_402delAGAG) was detected in 15 patients from 10 families. This mutation was associated with a large spectrum of phenotypes from type I to asymptomatic patients. Five patients from two consanguineous families were homozygous for the mutation with diverse mild phenotypes. Determination of the SMN2 copy number showed that the presence of two or three copies generally correlated with a better evolution. RT-PCR studies of SMN transcripts in control and patients with the same SMN2 copy number showed that the full-length/Delta7 ratio is influenced by the SMN1 genotype although it seems independent of the SMN2 copy number. Moreover, protein analysis in these patients showed a reduction in SMN protein in compound heterozygous patients (c.399_402delAGAG/deletion) when compared with homozygous c.399_402delAGAG/c.399_402delAGAG patients. Microsatellite DNA markers flanking the SMA locus revealed the occurrence of the 4-bp deletion in the background of the same haplotype, suggesting that a single mutational event was involved in the 10 families. The geographic origins of ancestors point to a founder effect from the south and east of Spain. The c.399_402delAGAG, which is to date unique to the Spanish population, constitutes the most frequently found subtle mutation in SMA. Hum Mutat 22:136-143, 2003.

Background Previously, we described a new variant of endemic pemphigus foliaceus (EPF) in Colombia, South America (El Bagre-EPF). Objective Continuing our characterization of this variant of EPF, we now focus on one of our previously reported clinical findings: the presence of ocular lesions. These ocular lesions are seen in patients having extensive skin involvement, as measured by the Lund and Browder scale, which is generally used for patients with skin burns. Methods We specifically searched for evidence of autoreactivity to various eyelid structures in these patients and correlated our immunologic data with the clinical findings. We performed indirect immunofluorescence studies using normal-appearing human eyelid skin from routine blepharoplasties as substrate tissue. We tested sera from 12 patients with El Bagre-EPF and ocular lesions, 5 patients with sporadic (nonendemic) pemphigus foliaceus, and 20 healthy control subjects (10 from the El Bagre-EPF endemic area and 10 from nonendemic areas). We used fluorescein isothiocyanate conjugated goat antiserum to human total IgG/IgA/IgM as a secondary antibody. In addition, we used fluorescein isothiocyanate conjugated antibodies to human fibrinogen, albumin, IgG, IgE, C1q, and C3, Texas Red (Rockland Immunochemicals, Inc, Gilbertsville, PA), Alexa Fluor 555, or Alexa Fluor 594 (Invitrogen, Carlsbad, CA). Ki-67 (a cell proliferation marker) was used to determine the cell proliferation rate, and nuclear counterstaining was performed with either 4′, 6-diamidino-2-phenylindole or Topro III (Invitrogen, Carlsbad, CA). Results We observed autoreactivity to multiple eyelid structures, including meibomian glands and tarsal muscle bundles at different levels, and some areas of the epidermis and the dermis close to the isthmus of the eyelids. Tarsal plate autoreactivity was seen in 10 of 12 of the El Bagre-EPF sera and in one control with pemphigus erythematosus. Furthermore, immunoprecipitation using an eyelid sample as a

Laminopathies, a group of heterogeneous disorders associated with lamin A/C gene (LMNA) mutations, encompass a wide spectrum of clinical phenotypes, which may present as separate disease or as overlapping syndromes. We describe a 35-year-old female in whom a novel sporadic heterozygous mutation c.1001_1003delGCC (p.Ser334del) of the LMNA gene was found. The patient presented with overlapping syndrome of heart failure secondary to dilated cardiomyopathy, limb-girdle dystrophy and partial lipodystrophy. Endomyocardial biopsy revealed strong up-regulation of HLA classes I and II antigens on microvessels and induction of the class I antigens on cardiomyocytes. On muscle biopsy, a wide range of fiber sizes and small clusters of inflammatory infiltrations were found. In the rapid progression of heart failure with arrhythmias or conduction defect, accompanied with muscle atrophy and lipodystrophy, the genetic disease should be taken into consideration. In addition, undefined inflammatory response and fibrosis in the heart or skeletal muscle might further justify screening of the lamin A/C gene.

Facioscapulohumeral muscular dystrophy (FSHD) is a common type of adult muscular dystrophy and is divided into types 1 and 2 based on genetic mutation. Clinically, both FSHD types often show asymmetric and progressive muscle weakness affecting initially the face, shoulder, and arms followed by the distal then proximal lower extremities. Approximately 95% of patients, termed FSHD1, have a deletion of a key number of repetitive elements on chromosome 4q35. The remaining 5%, termed FSHD2, have no deletion on chromosome 4q35. Nevertheless, both types share a common downstream mechanism, making it possible for future disease-directed therapies to be effective for both FSHD types.

Duchenne muscular dystrophy, an X-linked disorder, has an incidence of one in 5000 boys and presents in early childhood with proximal muscle weakness. Untreated boys become wheelchair bound by the age of 12 years and die of cardiorespiratory complications in their late teens to early 20s. The use of corticosteroids, non-invasive respiratory support, and active surveillance and management of associated complications have improved ambulation, function, quality of life and life expectancy. The clinical features, investigations and management of Duchenne muscular dystrophy are reviewed, as well as the latest in some of the novel therapies.

Monitoring turbidity and Surface Suspended Sediment Concentration (SSSC) of inland waters in tropics is essential to assess human health risks, in particular the diarrheal disease risk. In this study, we explore the use of Spot5 time series acquired for the Spot5Take5 Program to monitor turbidity and SSSC on the Bagre Lake (Burkina Faso). Field measurements (turbidity, SSSC, radiometry) are used to evaluate different radiometric indices. The combination of the NIR with a visible band (R or G) is found to be the best suited to retrieve SSSC and turbidity from Spot5 images. Large differences between upstream and downstream areas of the lake are well capture by the Spot5 time series, with large difference in the seasonal maximum both for absolute values and timing. A large sediment transport is observed from upstream to downstream between June and September caused by surface runoff and erosion. The high turbidity values observed suggest that the associated health hazard is potentially high, especially at the beginning of the rainy season and in the upstream areas of the lake.

... are most often affected. Complications include scoliosis and chronic shortening of muscles or tendons around joints. × Definition Spinal Muscular Atrophy (SMA) Types I, II, and III belong to a group of hereditary diseases that cause weakness and wasting of the voluntary muscles in the arms and ...

Facioscapulohumeral muscular dystrophy (FSHD), a dominantly inherited disorder, is the third most common dystrophy after Duchenne and myotonic muscular dystrophy. No known effective treatments exist for FSHD. The lack of an understanding of the underlying pathophysiology remains an obstacle in the development of targeted therapeutic interventions. The genetic defect is a loss of a critical number of a repetitive element (D4Z4) in the 4q subtelomeric region. The loss of the repeats results in specific changes in chromatin structure, although neither the molecular nor the cellular consequences of this change are known. Nevertheless, these epigenetic changes in chromatin structure offer a potential therapeutic target. This review discusses current management strategies in FSHD as well as potential therapeutic interventions to slow down or reverse the progressive muscle atrophy and weakness.

A significant correlation exists between the concentration of parasites, bacteria and some water quality parameters including surface suspended solids (SSS) and turbidity. Suspended particles can carry viruses and pathogenic bacteria affecting human health and foster their development. High SSS, associated with high turbidity, can therefore be considered as a vector of microbiological contaminants, causing diarrheal diseases. Few studies have focused on the turbidity parameter in rural Africa, while many cases of intestinal parasitic infections are due to the consumption of unsafe water from ponds, lakes, and rivers. Monitoring turbidity may therefore contribute to health hazard monitoring. Turbidity refers to the optical properties of water and is known to impact water reflectance in the visible and near-infrared domain. Ideally, its spatial and temporal variability requires the use of high temporal resolution (MODIS) and spatial resolution (Landsat, SPOT, Sentinel-2). Here we investigate turbidity in West-Africa. Various algorithms and indices proposed in the literature for inland waters are applied to MODIS series and to Landsat 7 and 8 CDR images, and SPOT5 images. The data and algorithms are evaluated with field measurements: turbidity, SSS, and hyperspectral ground radiometry. We show that turbidity of the Bagre Lake displays a strong increase over 2000-2015, associated with the corresponding increase of the red and NIR reflectances, as well as a reduction of the seasonal variations. Water level derived from the Jason 2 altimeter does not explain such variations. The most probable hypothesis is a change in land use (increase in bare and degraded soils), that leads to an increase in the particles transported by surface runoff to the lake. Such an increase in turbidity reinforces the health risk. We will discuss the link between turbidity and health in view of data from health centers on diarrheal diseases as well as data on practices and uses of populations.

Background: We reported a new variant of endemic pemphigus foliaceus in El Bagre, Colombia. Aims: Our study performed Complex Segregation Analysis (CSA) and short tandem repeats to discriminate between environmental and/or genetic factors in this disorder. Materials and Methods: The CSA analysis was carried out according to the unified model, implemented using the transmission probabilities implemented in the computer program POINTER, and evaluated by using a software package for population genetic data analysis (GDA), Arlequin. We performed pedigree analyses by using Cyrillic 2.1 software, with a total of 30 families with 50 probands (47 males and 3 females) tested. In parallel to the CSA, we tested for the presence of short tandem repeats from HLA class II, DQ alpha 1, involving the gene locus D6S291 by using the Hardy-Weinberg- Castle law. Results Our results indicate that the best model of inheritance in this disease is a mixed model, with multifactorial effects within a recessive genotype. Two types of possible segregation patterns were found; one with strong recessive penetrance in families whose phenotype is more Amerindian-like, and another of possible somatic mutations. Conclusion: The penetrance of 10% or less in female patients 60 years of age or older indicates that hormones could protect younger females. The greatest risk factor for men being affected by the disorder was the NN genotype. These findings are only possible due to somatic mutations, and/or strong environmental effects. We also found a protective role for two genetic loci (D6S1019 AND D6S439) in the control group. PMID:22666691

Congenital muscular torticollis (CMT) is a rare congenital musculoskeletal disorder characterized by unilateral shortening of the sternocleidomastoid muscle (SCM). It presents in newborn infants or young children with reported incidence ranging from 0.3% to 2%. Owing to effective shortening of SCM on the involved side there is ipsilateral head tilt and contralateral rotation of the face and chin. This article reports a case of CMT in a 3½-year-old male child successfully managed by surgical release of the involved SCM followed by physiotherapy. PMID:24205484

In the mid-sixties, Gary Graham, a Boeing designer, developed a cardiovascular conditioner for a planned Air Force orbiting laboratory. After the project was cancelled, Graham participated in space station conditioning studies for the Skylab program. Twenty years later, he used this expertise to develop the Shuttle 2000-1, a physical therapy and athletic development conditioner, available through Contemporary Designs. The machine is used by football teams, sports clinics and medical rehabilitation centers. Cardiovascular fitness and muscular strength development are promoted through both kinetic and plyometric exercises.

The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Each of these disorders represents a different class of genetic disease (monogenic, epigenetic, and repeat expansion disorders), and the approach to therapy addresses the diverse and complex molecular mechanisms involved in these diseases. The large number of novel pharmacologic agents in development with good biologic rationale and strong proof of concept suggests there will be an improved quality of life for individuals with muscular dystrophy. PMID:23939629

Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ambulance and cardiac and respiratory failure. A number of molecular processes have now been identified which hasten disease progression in human patients and animal models of muscular dystrophy. Accumulating evidence further suggests that aberrant activation of several signaling pathways aggravate pathological cascades in dystrophic muscle. Although replacement of defective gene with wild-type is paramount to cure, management of secondary pathological changes has enormous potential to improving the quality of life and extending lifespan of muscular dystrophy patients. In this article, we have reviewed major cellular and molecular mechanisms leading to muscle wasting in muscular dystrophy. PMID:23669245

Alternative splicing of pre-mRNAs is a major contributor to proteomic diversity and to the control of gene expression in higher eukaryotic cells. For this reasons, alternative splicing is tightly regulated in different tissues and developmental stages and its disruption can lead to a wide range of human disorders. The aim of this review is to focus on the relevance of alternative splicing for muscle function and muscle disease. We begin by giving a brief overview of alternative splicing, muscle-specific gene expression and muscular dystrophy. Next, to illustrate these concepts we focus on two muscular dystrophy, myotonic muscular dystrophy and facioscapulohumeral muscular dystrophy, both associated to disruption of splicing regulation in muscle. PMID:20603608

Background: The demographic development with an ageing population is predicted to be the next global public health challenge. Advances in medicine and the socioeconomic development have reduced mortality and morbidity due to infectious conditions and non-communicable diseases. The increase in longevity will not be restricted to healthy people. Objective: To understand how people with muscular diseases experience ageing. Method: A literature review was conducted using the Matrix Method developed by Garrard (2007). This systematic method was used to identify, describe and interpret studies, irrespective of the methods applied. To avoid the exclusion of important sources, experiences and topics, we chose an integrative approach that accommodates the inclusion of studies with different methodologies. People with MD have gradually extended their life expectancy during the last 30 years. Thus, we reviewed the literature regarding MD and ageing without time limit. Results: We identified three themes: 1) Slowing down early 2) Accepting lifelong deterioration and 3) Striving for normality. Conclusion: People with MD live in a field of tension between a feeling of autonomy and normality and difficulties coping with reduced physical abilities. Getting older accentuates this tension since the physical strength diminishes and it is harder to maintain autonomy. The bodily challenges may coincide with the end of the rehabilitation people living with MD have received. Seemingly, no age-related rehabilitation is offered, and people living with MD are thus at risk of an unnecessarily passive life. PMID:28144383

A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic

Turner syndrome is a relatively common chromosomal disorder which affects about one in 2000 live born females. Duchenne muscular dystrophy is an X-linked recessive disorder affecting 1:3600 live born males. Considering the above, the coexistence of these two diseases may occur only anecdotally. Here, we report a 4 ½ year-old female with classical 45,X Turner syndrome who also had Duchenne muscular dystrophy caused by a point mutation in the dystrophin gene (c.9055delG). The patient showed the typical phenotype of Turner syndrome including distinctive dysmorphic features (short neck, low posterior hairline, wide position of nipples), aortic coarctation and feet lymphedema. Besides, she presented with an unusually early beginning of muscular dystrophy symptoms with infantile-onset motor developmental delay, intellectual disability and early calf muscular hypertrophy. The coexistence of an X-linked recessive disorder should be considered in women affected by Turner syndrome presenting with additional atypical clinical features.

Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ambulance and cardiac and respiratory failure. A number of molecular processes have now been identified which hasten disease progression in human patients and animal models of muscular dystrophy. Accumulating evidence further suggests that aberrant activation of several signaling pathways aggravate pathological cascades in dystrophic muscle. Although replacement of defective gene with wild-type is paramount to cure, management of secondary pathological changes has enormous potential to improving the quality of life and extending lifespan of muscular dystrophy patients. In this article, we have reviewed major cellular and molecular mechanisms leading to muscle wasting in muscular dystrophy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

Chronic spinal muscular atrophy of FSH type affecting a mother and her son and daughter is reported. The relevant literature is reviewed and the relation between this conditon and Kugelberg-Welander (K-W) disease is discussed. Chronic spinal muscular atrophy of FSH type is considered to be a different entity from the eponymous K-W disease. Each type of muscular dystrophy, e.g. limb-girdle, FSH, distal, ocular, or oculopharyngeal type, has its counterpart of nuclear origin. A classification of the chronic spinal muscular atrophies is suggested following the classification of muscular dystrophy. Images PMID:957378

Respiratory failure is a major contributor to immobility and mortality in progressive muscular dystrophies. The severity of pulmonary impairment and the stage at which it develops differ according to the type of muscular dystrophy. Appropriate respiratory management for each type should be considered. In Duchenne muscular dystrophy (DMD), respiratory impairment manifests in the late teens, and assisted mechanical ventilation is administered. Noninvasive positive-pressure ventilation (NIPPV) has increased the median survival of patients with DMD by 10 year and improved quality of life. In myotonic dystrophy (MyD), the causes of respiratory failure can involve both the central and the peripheral nervous systems in addition to respiratory muscles. Nocturnal desaturation is more severe in MyD than in other muscular dystrophies with similar degrees of respiratory muscle weakness. Cognitive impairment should be taken into account in the management of MyD patients. NIPPV does not appear to improve survival of MyD. Guidelines for DMD have been published. Respiratory function should be assessed serially by measuring forced vital capacity, oxyhemoglobin saturation, peak cough flow, and end-tidal CO2 level. A respiratory action plan should be enacted with increasing disease severity. Therapeutic measures comprise airway clearance, respiratory muscle training, noninvasive nocturnal ventilation, daytime noninvasive ventilation, and continuous invasive ventilation. At the advanced stage of respiratory failure, attention should be paid to complications related to long-term mechanical ventilation, such as pneumothorax and tracheal hemorrhage. Discussing about end-of-life care among the patient, family, and physician is important before mechanical ventilatory support is required.

This study investigated age-related differences in muscular strength and muscular endurance among 73 female masters swimmers aged 24 to 71 years. While an age-related decline in muscular strength was apparent, the results failed to reveal a similar trend for endurance, suggesting that swimming influences endurance more than strength among women.…

This study investigated age-related differences in muscular strength and muscular endurance among 73 female masters swimmers aged 24 to 71 years. While an age-related decline in muscular strength was apparent, the results failed to reveal a similar trend for endurance, suggesting that swimming influences endurance more than strength among women.…

Examined the validity of field tests of elementary students' upper body muscular strength and endurance. Field tests were found to be moderately valid measures of weight-relative muscular strength but not of absolute strength and muscular endurance. (SM)

Examined the validity of field tests of elementary students' upper body muscular strength and endurance. Field tests were found to be moderately valid measures of weight-relative muscular strength but not of absolute strength and muscular endurance. (SM)

Forty children with hypotonia and non progressive cerebral impairment were observed. In all cases muscle morpho-histometric and ultrastructural studies were performed, in 13 cases muscular acetylcholinesterase study was carried out. The Authors pointed out the high frequency (92% of cases) of muscle abnormalities: histochemical alteration of fibre type distribution (type 1 or type 2 fibres prevalence, type 2C persistence), diameter change (hypertrophy or hypotrophy of the fibres). In 37.5% of the cases, randomly distributed, were also present myofibrillar degeneration, Z band streaming, desalignment or marked destructuration of the sarcomeres. The muscular acetylcholinesterase study showed the same anomalous pattern of molecular forms (11 out of 13 cases), with increase of light (6S, 4S) and disappearance of heavy (16S) and medium forms (13S, 10S), without significant change of enzymatic activity. The possible alterated influence of CNS on muscle fibre differentiation and growth because of abnormal neural control is discussed. This hypothesis even if could be related with abnormal fibre typing and diameter, do not seem to explain the ultrastructural and biochemical abnormalities observed.

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From the clinical and genetic point of view, congenital muscular dystrophies (CMD) are a heterogenic group of diseases within neuromuscular pathologies. The best known forms are: merosin deficiency CMD, collagen VI deficiency CMD, LMNA-related CMD, selenoprotein-related CMD (SEPN1) and alpha-dystroglycan-related CMD. They present with a broad spectrum of clinical phenotypes. Most of them are transmitted by recessive autosomal inheritance. The initial manifestations very often begin in infancy or in the neonatal period. There are clinical suspicions of the existence of hypotonia and paresis, and they are characterised by a dystrophic pattern in the muscular biopsy (muscle replaced by fibroadipose tissue, with necrosis and cell regeneration). Advances in the understanding of the molecular pathogenesis of CMD have made it possible to make further progress in the classification of the different subtypes. The aim of this review is to comment on the advances made in recent years as regards the classification of CMD in terms of genetics, the proteins involved and their clinical presentation.

The genetic basis of many muscular disorders, including many of the more common muscular dystrophies, is now known. Clinically, the recent genetic advances have improved diagnostic capabilities, but they have not yet provided clues about treatment or management. Thanks to better management strategies and therapeutic interventions, however, many patients with a muscular dystrophy are more active and are living longer. Physical therapists, therefore, are more likely to see a patient with a muscular dystrophy, so understanding these muscle disorders and their management is essential. Physical therapy offers the most promise in caring for the majority of patients with these conditions, because it is unlikely that advances in gene therapy will significantly alter their clinical treatment in the near future. This perspective covers some of the basic molecular biological advances together with the clinical manifestations of the muscular dystrophies and the latest approaches to their management. PMID:16305275

Muscular dystrophies are a heterogeneous group of hereditary diseases characterized by loss of muscle and weakness of non neurogenic origin. They are caused by mutations in one or more genes involved in the formation of muscle cells. The discovery of several proteins in the muscle began with the discovery of dystrophin, 130 years after the clinical description of muscular dystrophy. Currently, due to a better understanding of the biology of normal and diseased muscle, has achieved a classification at the molecular level of different types of muscular dystrophies, according to the protein that is affected. This has been particularly important for limb girdle muscular dystrophies, which present clinical features that can lead to confusion with Duchenne muscular dystrophy. Moreover, in recent years has encouraged the development of therapies in the near future could provide a solution for restoring the function of the muscle fiber.

Muscular dystrophies are a group of diseases characterised by the primary wasting of skeletal muscle, which compromises patient mobility and in the most severe cases originate a complete paralysis and premature death. Existing evidence implicates calcium dysregulation as an underlying crucial event in the pathophysiology of several muscular dystrophies, such as dystrophinopathies, calpainopathies or myotonic dystrophy among others. Duchenne muscular dystrophy is the most frequent myopathy in childhood, and calpainopathy or LGMD2A is the most common form of limb-girdle muscular dystrophy, whereas myotonic dystrophy is the most frequent inherited muscle disease worldwide. In this review, we summarise recent advances in our understanding of calcium ion cycling through the sarcolemma, the sarcoplasmic reticulum and mitochondria, and its involvement in the pathogenesis of these dystrophies. We also discuss some of the clinical implications of recent findings regarding Ca2+ handling as well as novel approaches to treat muscular dystrophies targeting Ca2+ regulatory proteins.

Spinal muscular atrophy is the most common fatal hereditary disease among newborns and infants. There is as yet no effective treatment. Although a carrier test is available, currently there is disagreement among professional medical societies who proffer standards of care as to whether or not carrier screening for spinal muscular atrophy should be offered as part of routine reproductive care. This leaves health care providers without clear guidance. In fall 2009, a meeting was held by National Institutes of Health to examine the scientific basis for spinal muscular atrophy carrier screening and to consider the issues that accompany such screening. In this article, the meeting participants summarize the discussions and conclude that pan-ethnic carrier screening for spinal muscular atrophy is technically feasible and that the specific study of implementing a spinal muscular atrophy carrier screening program raises broader issues about determining the scope and specifics of carrier screening in general. PMID:20808230

Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. Key points A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination. In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia. Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness. Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase. The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and

Muscular dystrophy is a genetic disorder leading to progressive weakness of muscles caused due to dysfunction in or lack of protein in muscle cells. The prevalence of muscular dystrophy has been observed globally and is becoming a critical area of study for better health services. The purpose of the study is to analyze the research strength of muscular dystrophy using bibliographic literature. A quantitative literature analysis was carried out on muscular dystrophy from 1991 to 2015 for assessing the global research trends. This literature-based study was conducted using the documents retrieved from the Science Citation Index using the keywords: Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), Congenital Muscular Dystrophy (CMD), Myotonic Dystrophy, Emery-Dreifuss Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Oculopharyngeal Muscular Dystrophy, and Limb-Girdle Muscular Dystrophy. Analysis was done for annual productivity of publication, authorship, collaboration, country performance, citation frequency, characteristics of most cited document, journal productivity, etc.

Receptor-activator of NF-κB, its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Although there is a strong association between osteoporosis and skeletal muscle atrophy/dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology still is elusive. Here, we show that muscle cells can produce and secrete osteoprotegerin and pharmacologic treatment of dystrophic mdx mice with recombinant osteoprotegerin muscles. (Recombinant osteoprotegerin-Fc mitigates the loss of muscle force in a dose-dependent manner and preserves muscle integrity, particularly in fast-twitch extensor digitorum longus.) Our data identify osteoprotegerin as a novel protector of muscle integrity, and it potentially represents a new therapeutic avenue for both muscular diseases and osteoporosis.

The muscular dystrophies (MDs) represent a diverse collection of inherited human disorders, which affect to varying degrees skeletal, cardiac, and sometimes smooth muscle (Emery, 20021). To date, more than 50 different genes have been implicated as causing one or more types of MD (Bansal et al., 20032). In many cases, invaluable insights into disease mechanisms, structure and function of gene products, and approaches for therapeutic interventions have benefited from the study of animal models of the different MDs (Arnett et al., 20093). The large number of genes that are associated with MD and the tremendous number of animal models that have been developed preclude a complete discussion of each in the context of this review. However, we summarize here a number of the more commonly used models together with a mixture of different types of gene and MD, which serves to give a general overview of the value of animal models of MD for research and therapeutic development. PMID:22137430

Muscular diseases lead to muscle fiber degeneration, impairment of mobility, and in some cases premature death. Many of these muscular diseases are largely idiopathic. The goal of this study was to identify biomarkers based on their functional role and possible mechanisms of pathogenesis, specific to individual muscular disease. We analyzed the muscle transcriptome from five major muscular diseases: acute quadriplegic myopathy (AQM), amyotrophic lateral sclerosis (ALS), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), dermatomyositis (DM) and polymyositis (PM) using pairwise statistical comparison to identify uniquely regulated genes in each muscular disease. The genome-wide information encoded in the transcriptome provided biomarkers and functional insights into dysregulation in each muscular disease. The analysis showed that the dysregulation of genes in forward membrane pathway, responsible for transmitting action potential from neural excitation, is unique to AQM, while the dysregulation of myofibril genes, determinant of the mechanical properties of muscle, is unique to ALS, dysregulation of ER protein processing, responsible for correct protein folding, is unique to DM, and upregulation of immune response genes is unique to PM. We have identified biomarkers specific to each muscular disease which can be used for diagnostic purposes.

Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein dystrophin. This disease has been studied using a variety of animal models including fish, mice, rats, and dogs. While these models have contributed substantially to our mechanistic understanding of the disease and disease progression, limitations inherent to each model have slowed the clinical advancement of therapies, which necessitates the development of novel large-animal models. Several porcine dystrophin-deficient models have been identified, although disease severity may be so severe as to limit their potential contributions to the field. We have recently identified and completed the initial characterization of a natural porcine model of dystrophin insufficiency. Muscles from these animals display characteristic focal necrosis concomitant with decreased abundance and localization of dystrophin-glycoprotein complex components. These pigs recapitulate many of the cardinal features of muscular dystrophy, have elevated serum creatine kinase activity, and preliminarily appear to display altered locomotion. They also suffer from sudden death preceded by EKG abnormalities. Pig dystrophinopathy models could allow refinement of dosing strategies in human-sized animals in preparation for clinical trials. From an animal handling perspective, these pigs can generally be treated normally, with the understanding that acute stress can lead to sudden death. In summary, the ability to create genetically modified pig models and the serendipitous discovery of genetic disease in the swine industry has resulted in the emergence of new animal tools to facilitate the critical objective of improving the quality and length of life for boys afflicted with such a devastating disease.

Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cell therapy and the use of granulocyte colony-stimulating factor (G-CSF) in muscular dystrophy was performed. PMID:26136844

Latent transforming growth factor-β (TGFβ) binding proteins (LTBPs) bind to inactive TGFβ in the extracellular matrix. In mice, muscular dystrophy symptoms are intensified by a genetic polymorphism that changes the hinge region of LTBP, leading to increased proteolytic susceptibility and TGFβ release. We have found that the hinge region of human LTBP4 was also readily proteolysed and that proteolysis could be blocked by an antibody to the hinge region. Transgenic mice were generated to carry a bacterial artificial chromosome encoding the human LTBP4 gene. These transgenic mice displayed larger myofibers, increased damage after muscle injury, and enhanced TGFβ signaling. In the mdx mouse model of Duchenne muscular dystrophy, the human LTBP4 transgene exacerbated muscular dystrophy symptoms and resulted in weaker muscles with an increased inflammatory infiltrate and greater LTBP4 cleavage in vivo. Blocking LTBP4 cleavage may be a therapeutic strategy to reduce TGFβ release and activity and decrease inflammation and muscle damage in muscular dystrophy.

... more common in particular ethnic groups? Genetic Changes Mutations in the TTN gene cause tibial muscular dystrophy . ... in chemical signaling and in assembling new sarcomeres. Mutations in the TTN gene alter the structure and ...

Although researchers have examined the negative effects of viewing reality television (RTV) on women's body image, this research has not been extended to men. Exploring the extent to which RTV depicts men who embody the muscular ideal may enhance our understanding of the potential influence of this media genre. We explored the extent to which RTV depicted men who embodied the muscular ideal using a quantitative content analysis. Based on binomial tests, the primary male cast members of programs airing on networks popular among young adult men during the Fall 2009 broadcast season were more muscular, with lower levels of body fat, than average U.S. men. The chest-to-waist and shoulder-to-waist ratios of these cast members did not differ as a function of program type (i.e., reality drama, endurance, and romance). Young men who view RTV programs included in the present study would be exposed to an unrepresentative muscular ideal. Published by Elsevier Ltd.

... section. How do people cope with muscular dystrophy (MD)? Although MD presents many challenges in many different aspects of daily life, those with MD enjoy full lives. Advances in drug therapies, physical ...

A new tool for muscular strength development by electromagnetic stimulation (MS) of muscular during voluntary contraction has been described. 18 healthy subjects (men) took part in the research. They were devided into two groups--control (CG) and experimental (EG). Subjects of CG and EG have equal muscular strength parameters. M. gastrocnemius of subjects in EG was exposed to MS (1.8 T, 5 Hz) during training exercises (plantar foot flection). The subjects of CG did not receive MS. The torque of plantar foot flection of EG subjects increased significantly (24%) during 10 days training. The torque of plantar foot flection of CG subjects did not change significantly. We hypothesize increasing of muscular strength of EG subjects was result of high-threshold motor units activation under MS.

Duchenne muscular dystrophy is a well defined form of sex linked inherited muscular disease. Approximately 1/3 of cases are the product of a new mutation. We studied 20 patients with this disease and 19 heterozygous females. Ceruloplasmin levels were significantly higher in patients compared to controls. A possible protective role of this enzyme against oxydating agents may help prevent peroxydation of lipids from the smooth muscle cell membrane.

This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group. PMID:27757431

Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3,500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child's quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.

Muscular fatigue can be defined as the failure to maintain an expected power output. It is a multifaceted phenomenon that incorporates metabolic, neural and neuromuscular components, among others. Metabolic causes of fatigue are associated with the ability to maintain energy supply during exercise, the speed at which homeostasis is achieved post-exercise, and the effects of high intensity exercise by-products on the peripheral neuromuscular system. Research has indicated that the central nervous system plays a protective role in preventing catastrophic muscle damage by reducing the intensity and frequency of propagation founded on biofeedback from the muscle cells. The duration and particularly the type of physical activity play a role in the development of muscle fatigue, with impact or weightbearing exercises, such as dance, producing increased symptoms compared to non-impact or non-weightbearing equivalents. The effects of prolonged exercise and the associated increased levels of muscle fatigue that may lead to compromises in neuromuscular propagation need to be considered in dance.

The purpose of this study was to evaluate the potential association of muscular strength and endurance at baseline with the prevalence of functional limitations at follow-up. Study participants were 3,069 men and 589 women (30-82 yr) who received a clinical examination including a strength evaluation at the Cooper Clinic between 1980 and 1989 and responded to a 1990 mail-back survey. Participants also had to achieve at least 85% of their age-predicted maximal heart rate on a maximal exercise treadmill test and have no history of heart attack, stroke, diabetes, high blood pressure, cancer, or arthritis at their first visit. A strength index composite score (0-6) was calculated using age- and sex-specific tertiles from bench press, leg press, and sit-up tests. Those scoring 5 or 6 were categorized in the high strength group. Functional health status was assessed by responses to questions about the participant's ability to perform light, moderate, and strenuous recreational, household, daily living, and personal care tasks. After an average follow-up of 5 yr, 7% of men and 12% of women reported at least one functional limitation. A logistic regression model including age, aerobic fitness, body mass index, and new health problems at follow-up found that, relative to those with lower levels of strength, the odds of reporting functional limitations at follow-up in men and women categorized as having higher levels of strength were 0.56 (95%CI = 0.34, 0.93) and 0.54 (95%CI = 0.21, 1.39), respectively. These findings, if replicated in other populations, suggest that maintenance of strength throughout the lifespan may reduce the prevalence of functional limitations.

Abstract Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and/or biomarkers. High throughput – omic technologies have provided a comprehensive understanding of the changes occurring in dystrophic muscles. Murine and canine animal models have been a valuable source to profile muscles and body fluids, thus providing candidate biomarkers that can be evaluated in patients. This review will illustrate known circulating biomarkers that could track disease progression and response to therapy in patients affected by Duchenne muscular dystrophy. We present an overview of the transcriptomic, proteomic, metabolomics and lipidomic biomarkers described in literature. We show how studies in muscle tissue have led to the identification of serum and urine biomarkers and we highlight the importance of evaluating biomarkers as possible surrogate endpoints to facilitate regulatory processes for new medicinal products. PMID:27858763

This is the first description of a dystrophin-Deficient muscular dystrophy in domestic cats. The disorder appears to be of X-linked inheritance because it affected both males of a litter of four kittens. Immunoblotting and immunofluorescent detection of dystrophin showed dystrophin present in control cat muscle but no detectable dystrophin in either affected cat. The feline muscular dystrophy was progressive and histopathologically resembled human Duchenne/Becker muscular dystrophy except for the lack of fat infiltration and the presence of prominent hypertrophy of both muscle fibers and muscles groups in the feline disorder. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9 PMID:2683799

Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments. PMID:27594988

The muscular dystrophies are a group of heterogeneous genetic diseases characterized by progressive degeneration and weakness of skeletal muscle. Since the discovery of the first muscular dystrophy gene encoding dystrophin, a large number of genes have been identified that are involved in various muscle-wasting and neuromuscular disorders. Human genetic studies complemented by animal model systems have substantially contributed to our understanding of the molecular pathomechanisms underlying muscle degeneration. Moreover, these studies have revealed distinct molecular and cellular mechanisms that link genetic mutations to diverse muscle wasting phenotypes. PMID:23671309

Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

A new method for surgical correction of Peyronie disease by grafting autologous muscular aponeurosis was tried in 4 patients. Early results were encouraging, with disappearance of penile curvature and of pain on erection. The urologist can perform the operation without the assistance a plastic surgeon must usually give when dermal grafts are used.

Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

Muscular metastases are exceptionally reported. The authors present a case of crural neuralgia in relation with a localisation in the psoas iliacus of a gastric carcinoma. A review of literature defines the rarity of this facts (156 cases) the etiology (carcinome more often) and the explication who is still obscur.

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. It is characterized by progressive muscle wasting and weakness of variable distribution and severity. Heart is involved leading to heart failure. Conduction abnormalities are unusual. We report a case of complete atrio-ventricular block in a DMD patient.

A common procedure in administering muscular endurance tests is to have several individuals perform the same task at the same time. A very old psychological concept known as social facilitation suggests that an individual's performance may be affected by the presence of others. (CK)

A common procedure in administering muscular endurance tests is to have several individuals perform the same task at the same time. A very old psychological concept known as social facilitation suggests that an individual's performance may be affected by the presence of others. (CK)

Objective: We provide a nationwide population study of patients with congenital muscular dystrophy in Italy. Methods: Cases were ascertained from the databases in all the tertiary referral centers for pediatric neuromuscular disorders and from all the genetic diagnostic centers in which diagnostic tests for these forms are performed. Results: The study includes 336 patients with a point prevalence of 0.563 per 100,000. Mutations were identified in 220 of the 336 (65.5%). The cohort was subdivided into diagnostic categories based on the most recent classifications on congenital muscular dystrophies. The most common forms were those with α-dystroglycan glycosylation deficiency (40.18%) followed by those with laminin α2 deficiency (24.11%) and collagen VI deficiency (20.24%). The forms of congenital muscular dystrophy related to mutations in SEPN1 and LMNA were less frequent (6.25% and 5.95%, respectively). Conclusions: Our study provides for the first time comprehensive epidemiologic information and point prevalence figures for each of the major diagnostic categories on a large cohort of congenital muscular dystrophies. The study also reflects the diagnostic progress in this field with an accurate classification of the cases according to the most recent gene discoveries. PMID:25653289

Duchenne muscular dystrophy is one of the best known forms of muscular dystrophy. The incidence in different countries varies from 130 to 390 per million male live births. Becker variety may be considered a mild form of Duchenne dystrophy, with an incidence 10 times lower. A sex linked recessive inheritance is involved in both forms, the affected gene is placed at locus X21. The incidence of both forms in Chile is similar to that reported worldwide, and has been increasing since 1950. Increased CK and LDH levels are confirmed in patients, and overall, they are also higher in female carriers. However only 26% of carriers have increased CK levels and 21% increased LDH levels, compared to normal subjects. Electromyograms show myopathic characteristics in all carrier women. The scope of a prospective clinical, genetic and epidemiologic study currently underway is discussed.

Duchenne muscular dystrophy is a devastating muscular dystrophy of childhood. Mutations in the dystrophin gene destroy the link between the internal muscle filaments and the extracellular matrix, resulting in severe muscle weakness and progressive muscle wasting. There is currently no cure and, whilst palliative treatment has improved, affected boys are normally confined to a wheelchair by 12 years of age and die from respiratory or cardiac complications in their twenties or thirties. Therapies currently being developed include mutation-specific treatments, DNA- and cell-based therapies, and drugs which aim to modulate cellular pathways or gene expression. This review aims to provide an overview of the different therapeutic approaches aimed at reconstructing the dystrophin-associated protein complex, including restoration of dystrophin expression and upregulation of the functional homologue, utrophin.

Congenital Muscular Torticollis (CMT) is a postural deformity of head and neck detected at birth or shortly after birth, primarily resulting from unilateral shortening of Sternocleidomastoid Muscle (SCM). In neonates and infants, patient may cure conservatively by physiotherapy but surgery is the treatment of choice for children and adolescents. There are various techniques of surgery. Here we show our experience regarding management of congenital muscular torticollis. In the present retrospective case series, fourteen patients of congenital muscular torticollis were treated. The cases were enrolled between Nov' 2005 to Oct' 2007 in Bangabandhu Sheikh Mujib Medical University, Gonosasthaya Somaj Vittik Medical College Hospital, Dhaka and different private clinics of Dhaka city of Bangladesh. Neonates and infants were treated conservatively with physiotherapy and others treated surgically by transection of both sternal and clavicular head of SCM under general anesthesia. Operated patients were released on following post operative day with advised to do physiotherapy. Patients age range from 7 days to 15 years of which ten were female and four male. SCM was shortened in all cases (8 on right side and 6 on left side). Eleven were female and three male. Of 14 patients, 2 neonates, 7 infants and 5 were more than 1 year age. There was no associated anomaly. Out of 9 neonates and infants 8 cured conservatively with physiotherapy and another one significantly improved. Six were treated surgically including one failed physiotherapy. Post operative period was uneventful and there was no complication. Results were evaluated clinically and comments of peers. Most of the patient of congenital muscular torticollis can be treated conservatively during infancy. Division of both sternal and clavicular head of SCM is easy and safe surgical technique for the treatment of CMT of older children and adolescents.

This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes.

This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes. PMID:28182029

Spinal muscular atrophy is one of the most common autosomal recessive diseases, affecting approximately one in 10,000 live births and with a carrier frequency of approximately one in 50. Spinal muscular atrophy is caused by a deficiency of the ubiquitous protein survival of motor neuron (SMN), which is encoded by the SMN genes, SMN1 and SMN2. Due to a single nucleotide polymorphism (840C>T), SMN2 produces less full-length transcript than SMN1 and cannot entirely prevent neuronal cell death at physiologic gene dosages. The 38-kDa SMN protein comprises 294 amino acids and is involved in the biogenesis of uridine-rich small nuclear ribonucleoproteins, facilitating their cytoplasmic assembly into the spliceosome. Various animal models have been developed to study the pathogenesis of spinal muscular atrophy, as well as to test novel therapeutics. Common PCR-restriction fragment length polymorphism assays can detect the homozygous absence of SMN1 in approximately 94% of patients with clinically typical spinal muscular atrophy. SMN gene dosage analysis can determine the copy number of SMN1 to detect carriers and patients heterozygous for the absence of SMN1. Due to the genetic complexity and the high carrier frequency, accurate risk assessment and genetic counseling are particularly important. Comprehensive SMA genetic testing, combined with appropriate genetic counseling and risk assessment, provides the most complete evaluation of patients and their families at this time. New technologies, such as monosomal analysis techniques, may be widely available in the future. Copyright Future Drugs Ltd.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. Muscle MRI identifies a specific pattern of muscle involvement in FSHD patients. Muscle MRI may predict FSHD in asymptomatic and severely affected patients. Muscle MRI of upper girdle better predicts FSHD. Muscle MRI may differentiate FSHD from other forms of muscular dystrophy. Muscle MRI may show the involvement of non-clinical testable muscles.

Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis. PMID:24581957

The effect of isometric muscular exertion on the human body was investigated by having subjects perform basic movements in a sitting position in the conventional manner with additional muscle tension at 50% maximum force and at maximum force. The pulse, arterial pressure, skin temperature, respiratory rate, minute respiratory volume and electrical activity of the muscles involved were all measured. Performance of the exercises with maximum muscular exertion for 20 sec and without movement resulted in the greatest shifts in these indices; in the conventional manner substantial changes did not occur; and with isometric muscular exertion with 50% maximum force with and without movement, optimal functional shifts resulted. The latter is recommended for use in industrial exercises for the prevention of hypodynamia. Ten exercises are suggested.

Two studies examined the threatened masculinity theory of male body dissatisfaction, which posits that threats to masculinity result in increased muscle dissatisfaction. In Study 1, a masculinity threat was followed by tasks examining confidence in physical ability and perceptions of current and ideal body shapes. Results showed that men who experienced a masculinity threat reported lower confidence in their physical ability and perceived themselves as less muscular than men who experienced an affirmation of their masculinity. In Study 2, men were asked to report their intention to increase muscularity and their appearance anxiety following a threat to masculinity. Results showed that men reported lower appearance anxiety and drive for muscularity when their masculinity was threatened than when their masculinity was affirmed. This apparent contradiction can be explained by noting that men may be motivated to deny appearance concerns following a threat to masculinity, as such concerns are equated with femininity.

Although research has found that body ideals presented by the media influence women's body dissatisfaction, less is known about media's influence on men's body satisfaction. An online survey examining media use, the drive for muscularity, and internalization of appearance and body shape ideals was given to a sample of 311 participants comprised of both men and women. Results indicated (a) the more time men and women reported watching television, the higher their reported drive for muscularity (b) total hours of viewing sports-related, image-focused, and entertainment television related to increased drive for muscularity in women (c) drive for muscularity in men related to watching image-focused television and reading men's health magazines, and (d) internalization of athletic attitudes towards appearance mediated the relationship between total television watched and drive for muscularity in both genders. Clinicians may wish to utilize these findings when treating men and women suffering from drive for muscularity and body dysmorphia.

Scoliosis occurs in nearly all non-ambulatory children with spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD). Non-operative treatments have not been shown to be effective at preventing progression of scoliosis. Progressive scoliosis can impact the ability of patients to sit comfortably, be cosmetically unappealing, and in severe cases exacerbate pulmonary disease. The main goal of operative treatment is to improve sitting balance and prevent progression of scoliosis. Complication rates are high and there is little data on effect of operative treatment on quality of life in children with SMA and DMD. Comprehensive multi-disciplinary pre-operative evaluations are vital to reduce the risks of operative treatment.

Pediatric neuromuscular disorders comprise a large variety of disorders that can be classified based on their neuroanatomical localization, patterns of weakness, and laboratory test results. Over the last decade, the field of translational research has been active with many ongoing clinical trials. This is particularly so in two common pediatric neuromuscular disorders: Duchenne muscular dystrophy and spinal muscular atrophy. Although no definitive therapy has yet been found, numerous active areas of research raise the potential for novel therapies in these two disorders, offering hope for improved quality of life and life expectancy for affected individuals. PMID:23634188

We used expression profiling to define the pathophysiological cascades involved in the progression of two muscular dystrophies with known primary biochemical defects, dystrophin deficiency (Duchenne muscular dystrophy) and α-sarcoglycan deficiency (a dystrophin-associated protein). We employed a novel protocol for expression profiling in human tissues using mixed samples of multiple patients and iterative comparisons of duplicate datasets. We found evidence for both incomplete differentiation of patient muscle, and for dedifferentiation of myofibers to alternative lineages with advancing age. One developmentally regulated gene characterized in detail, α-cardiac actin, showed abnormal persistent expression after birth in 60% of Duchenne dystrophy myofibers. The majority of myofibers (∼80%) remained strongly positive for this protein throughout the course of the disease. Other developmentally regulated genes that showed widespread overexpression in these muscular dystrophies included embryonic myosin heavy chain, versican, acetylcholine receptor α-1, secreted protein, acidic and rich in cysteine/osteonectin, and thrombospondin 4. We hypothesize that the abnormal Ca2+ influx in dystrophin- and α-sarcoglycan–deficient myofibers leads to altered developmental programming of developing and regenerating myofibers. The finding of upregulation of HLA-DR and factor XIIIa led to the novel identification of activated dendritic cell infiltration in dystrophic muscle; these cells mediate immune responses and likely induce microenvironmental changes in muscle. We also document a general metabolic crisis in dystrophic muscle, with large scale downregulation of nuclear-encoded mitochondrial gene expression. Finally, our expression profiling results show that primary genetic defects can be identified by a reduction in the corresponding RNA. PMID:11121445

Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by an expanded repeat in the androgen receptor gene. The mutant protein is toxic to motor neurons and muscle. The toxicity is ligand-dependent and likely involves aberrant interaction of the mutant androgen receptor with other nuclear factors leading to transcriptional dysregulation. Various therapeutic strategies have been effective in transgenic animal models, and the challenge now is to translate these strategies into safe and effective treatment in patients. PMID:26547319

Duchenne muscular dystrophy (DMD) is a common lethal disease for which no effective treatment is currently available. There exists a mouse model of the disease in which the usefulness of gene therapy was established. However, no progress towards human application was made due to the lack of a proper method for gene delivery. During the past several years, researchers acquired data which led them to believe that bone marrow stem cells are capable of generating not only blood cells, but also liver, heart, skin, muscle, and other tissue. Although the term "stem cell plasticity" became very popular, other studies have suggested that bone marrow might contain different types of stem cells that can produce non-hematopoietic cells. For example, mesenchymal stem cell (MSC) in bone marrow give rise to osteocytes, chondrocytes, adipocytes, and skeletal muscle. Recently, researchers have been able to show that transplanted bone marrow cells can contribute to muscle cells in a human patient who was diagnosed with two genetic diseases: severe combined immunodeficiency (SCID) and Duchenne muscular dystrophy. The odds of this happening is estimated at one in seven million. The results of studying this patient's medical history were reported by collaborating researchers at Children's Hospital, Los Angeles and Children's Hospital, Boston in an article titled "Long-term persistence of donor nuclei in a Duchenne muscular dystrophy (DMD) patient receiving bone marrow transplantation" published in the September 2002 issue of the Journal of Clinical Investigation. This patient was transplanted 15 years ago at Children's Hospital Los Angeles with paternal HLA-haploidentical T cell-depleted bone marrow. He engrafted and became a hematopoietic chimera having T and NK lymphocytes of donor origin. Studies performed on the muscle biopsy from the patient 13 years after transplantation demonstrated that the muscle showed evidence of donor derived nuclei. In addition, analysis of his bone marrow

Duchenne muscular dystrophy (DMD) is caused mostly by internal deletions in the gene for dystrophin, a protein essential for maintaining muscle cell membrane integrity. These deletions abrogate the reading frame and the lack of dystrophin results in progressive muscle deterioration. DMD patients experience progressive loss of ambulation, followed by a need for assisted ventilation, and eventual death in mid-twenties. By the method of exon skipping in dystrophin pre-mRNA the reading frame is restored and the internally deleted but functional dystrophin is produced. Two oligonucleotide drugs that induce desired exon skipping are currently in advanced clinical trials.

Cysticercosis is a parasitic disease caused by a worm of the Cestoda class. The most prevalent form affects the nervous system. This case report is from a 78-year-old female patient evaluated at Clínica Mult Imagem, in the city of Santos, Brazil, who presented a form of the disease that differed from the classic neurocysticercosis, in this case muscular cysticercosis. This and other forms of manifestation justify further studies to ensure adequate recognition, diagnosis and treatment of this parasitic disease.

Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. We previously showed that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and activator of the NAD(+)-dependent protein deacetylase SIRT1, delays the progression of heart failure and prolongs the lifespan of δ-sarcoglycan-deficient hamsters. Because a defect of dystroglycan complex causes muscular dystrophies, and δ-sarcoglycan is a component of this complex, we hypothesized that resveratrol might be a new therapeutic tool for muscular dystrophies. Here, we examined resveratrol's effect in mdx mice, an animal model of Duchenne muscular dystrophy. mdx mice that received resveratrol in the diet for 32 weeks (4 g/kg diet) showed significantly less muscle mass loss and nonmuscle interstitial tissue in the biceps femoris compared with mdx mice fed a control diet. In the muscles of these mice, resveratrol significantly decreased oxidative damage shown by the immunostaining of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine and suppressed the up-regulation of NADPH oxidase subunits Nox4, Duox1, and p47(phox). Resveratrol also reduced the number of α-smooth muscle actin (α-SMA)(+) myofibroblast cells and endomysial fibrosis in the biceps femoris, although the infiltration of CD45(+) inflammatory cells and increase in transforming growth factor-β1 (TGF-β1) were still observed. In C2C12 myoblast cells, resveratrol pretreatment suppressed the TGF-β1-induced increase in reactive oxygen species, fibronectin production, and expression of α-SMA, and SIRT1 knockdown blocked these inhibitory effects. SIRT1 small interfering RNA also increased the expression of Nox4, p47(phox), and α-SMA in C2C12 cells. Taken together, these findings indicate that SIRT1 activation may be a useful strategy for treating muscular dystrophies.

Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

Age-associated loss of muscular strength and muscular power are critical determinants of loss of physical function and progression to disability in older adults. In this study, we examined the association of systemic vascular function and measures of muscle strength and power in older adults. Measu...

This study examined the effects of contingent muscular tension on a choice reaction task, and especially, the effects various amounts of muscular tension have on the information processing of choice reaction time. The reactive movement task included a choice reaction task. Ten right-handed healthy men (ages 18 to 19 years) underwent trials with stimulus presentation probabilities of 50% and 20% on the muscular tension task and choice reaction tasks. The conditions for the muscular tension tasks were divided into seven different conditions: 0%, 10%, 20%, 30%, 40%, 50%, and 60% of maximum voluntary contraction. On these tasks, subjects performed isometric contraction of the biceps brachii. The choice reaction task was a rapid extension of the left or right knee as a choice reaction. Measures were choice reaction time, movement time, and total reaction time. Analysis indicated that shortening choice reaction time of the left and right feet was observed under 10% muscular tension of maximum strength. Muscular tension appreciably influenced information processing, including choice reaction time. Muscular tension did not affect movement time. Results are discussed with respect to previous research and the optimal muscular tension for best performance.

Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

The upper body muscular endurance of males and females 2-5 years of age was assessed, and relationships relative to sex, age, endurance and selected anthropometric measures were investigated. None of the relationships were found to be of practical predicative value; while upper body muscular strength increased with age, no significant differences…

In this investigation of congenital muscular torticollis, 311 infants treated consecutively for congenital torticollis over an 8-year period (1995-2003) at the Pediatric Neurology Clinic of Istanbul Medical Faculty, Istanbul University, Turkey were reviewed retrospectively. The clinical presentation, associated abnormalities, treatment, and outcomes of the overall group and of subgroups divided according to an ultrasonography-based classification were evaluated. All patients were evaluated using a standard approach: cervical ultrasonography was performed, and the patients were divided into two subgroups. Each group was scanned for other anomalies, and outcomes were compared. The mean age at diagnosis was 2.3 months; patients included in this study were 138 males and 173 females. Two clinical subgroups, comprised of sternomastoid tumors 85% and postural torticollis 15%, were identified. Passive range of motion was the initial treatment recommended for all of the patients. Follow-up data were available for all 311 patients; 95% experienced total resolution and 5% experienced subtotal resolution. We conclude that the majority of children with congenital muscular torticollis experience total resolution of symptoms. The success rate of conservative treatment is primarily dependent on the patients' age at the initiation of exercises and ultrasonographic findings.

Background In Facioscapulohumeral muscular dystrophy (FSHD), the upper girdle is early involved and often difficult to assess only relying on physical examination. Our aim was to evaluate the pattern and degree of involvement of upper girdle muscles in FSHD compared with other muscle diseases with scapular girdle impairment. Methods We propose an MRI protocol evaluating neck and upper girdle muscles. One hundred-eight consecutive symptomatic FSHD patients and 45 patients affected by muscular dystrophies and myopathies with prominent upper girdle involvement underwent this protocol. Acquired scans were retrospectively analyzed. Results The trapezius (100% of the patients) and serratus anterior (85% of the patients) were the most and earliest affected muscles in FSHD, followed by the latissimus dorsi and pectoralis major, whilst spinati and subscapularis (involved in less than 4% of the patients) were consistently spared even in late disease stages. Asymmetry and hyperintensities on short-tau inversion recovery (STIR) sequences were common features, and STIR hyperintensities could also be found in muscles not showing signs of fatty replacement. The overall involvement appears to be disease-specific in FSHD as it significantly differed from that encountered in the other myopathies. Conclusions The detailed knowledge of single muscle involvement provides useful information for correctly evaluating patients' motor function and to set a baseline for natural history studies. Upper girdle imaging can also be used as an additional tool helpful in supporting the diagnosis of FSHD in unclear situations, and may contribute with hints on the currently largely unknown molecular pathogenesis of this disease. PMID:24932477

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent forms of muscular dystrophy. The aims of this study were: 1) to evaluate the prevalence of sleep disordered breathing (SDB) in patients with FSHD; 2) to define the sleep-related respiratory patterns in FSHD patients with SDB; and 3) to find the clinical predictors of SDB. Fifty-one consecutive FSHD patients were enrolled, 23 women, mean age 45.7+/-12.3 years (range: 26-72). The diagnosis of FSHD was confirmed by genetic tests. All patients underwent medical and neurological evaluations, subjective evaluation of sleep and full-night laboratory-based polysomnography. Twenty patients presented SDB: 13 presented obstructive apneas, four presented REM related oxygen desaturations and three showed a mixed pattern. Three patients needed positive airways pressure. SDB was not related to the severity of the disease. Body mass index, neck circumference and daytime sleepiness did not allow prediction of SDB. In conclusion, the results suggest a high prevalence of SDB in patients with FSHD. The presence of SDB does not depend on the clinical severity of the disease. SDB is often asymptomatic, and no clinical or physical measure can reliably predict its occurrence. A screening of SDB should be included in the clinical assessment of FSHD.

Duchenne muscular dystrophy (DMD) is an X-linked hereditary dystrophinopathy due to the absence of dystrophin, a cytoskeleton protein; it is the most frequent of the dystrophinopathies. DMD affects one newborn boy in 3500. The disease locus is found on the short arm of the X chromosome (Xp21). Dystrophin plays an important role in the maintenance of the cellular architecture and permits signal transduction between the cytoskeleton and the extracellular matrix. Its absence is expressed by peripheral muscular damage, most often at the pelvic girdle, and sometimes associated with pseudohypertrophy of the calf. The disease is very often complicated by cardiac damage that develops towards the end of adolescence, together with restrictive lung disease that will usually end up requiring respiratory support. The prognosis is severe. Doppler examination of the myocardial tissue helps to screen for subclinical myocardial damage. Therapeutic management is multidisciplinary. Medical treatment of cardiac involvement relies on the drugs already proved effective in chronic heart failure. Ongoing research is currently studying gene therapy.

Background Mice from the MRL or “superhealing” strain have enhanced repair after acute injury to the skin, cornea, and heart. We now tested an admixture of the MRL genome and found that it altered the course of muscle pathology and cardiac function in a chronic disease model of skeletal and cardiac muscle. Mice lacking γ-sarcoglycan (Sgcg), a dystrophin-associated protein, develop muscular dystrophy and cardiomyopathy similar to their human counterparts with limb girdle muscular dystrophy. With disruption of the dystrophin complex, the muscle plasma membrane becomes leaky and muscles develop increased fibrosis. Methods MRL/MpJ mice were bred with Sgcg mice, and cardiac function was measured. Muscles were assessed for fibrosis and membrane leak using measurements of hydroxyproline and Evans blue dye. Quantitative trait locus mapping was conducted using single nucleotide polymorphisms distinct between the two parental strains. Results Introduction of the MRL genome reduced fibrosis but did not alter membrane leak in skeletal muscle of the Sgcg model. The MRL genome was also associated with improved cardiac function with reversal of depressed fractional shortening and the left ventricular ejection fraction. We conducted a genome-wide analysis of genetic modifiers and found that a region on chromosome 2 was associated with cardiac, diaphragm muscle and abdominal muscle fibrosis. Conclusions These data are consistent with a model where the MRL genome acts in a dominant manner to suppress fibrosis in this chronic disease setting of heart and muscle disease. PMID:23216833

Fibrosis is the main complication of muscular dystrophies. We identified moesin, a member of the ezrin-radixin-moesin family, in dystrophic muscles of mice representing Duchenne and congenital muscular dystrophies (DMD and CMD, respectively) and dysferlinopathy, but not in the wild type. High levels of moesin were also observed in muscle biopsy specimens from DMD, Ullrich CMD, and merosin-deficient CMD patients, all of which present high levels of fibrosis. The myofibroblasts, responsible for extracellular matrix protein synthesis, and the macrophages infiltrating the dystrophic muscles were the source of moesin. Moesin-positive cells were embedded within the fibrotic areas between the myofibers adjacent to the collagen type I fibers. Radixin was also synthesized by the myofibroblasts, whereas ezrin colocalized with the myofiber membranes. In animal models and patients' muscles, part of the moesin was in its active phosphorylated form. Inhibition of fibrosis by halofuginone, an antifibrotic agent, resulted in a major decrease in moesin levels in the muscles of DMD and CMD mice. In summary, the results of this study may pave the way for exploiting moesin as a novel target for intervention in MDs, and as part of a battery of biomarkers to evaluate treatment success in preclinical studies and clinical trials.

Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee.

Evolutionary scientists propose that exaggerated secondary sexual characteristics are cues of genes that increase offspring viability or reproductive success. In six studies the hypothesis that muscularity is one such cue is tested. As predicted, women rate muscular men as sexier, more physically dominant and volatile, and less committed to their mates than nonmuscular men. Consistent with the inverted-U hypothesis of masculine traits, men with moderate muscularity are rated most attractive. Consistent with past research on fitness cues, across two measures, women indicate that their most recent short-term sex partners were more muscular than their other sex partners (ds = .36, .47). Across three studies, when controlling for other characteristics (e.g., body fat), muscular men rate their bodies as sexier to women (partial rs = .49-.62) and report more lifetime sex partners (partial rs = .20-.27), short-term partners (partial rs = .25-.28), and more affairs with mated women (partial r = .28).

The present study tested the hypothesis that men's drive for muscularity would be associated with their valuation of domination, power, status, and aggression over others. A community sample of 359 men from London, UK, completed measures of drive for muscularity, social dominance orientation, right-wing authoritarianism, trait aggression, and need for power, as well as their demographic details. Bivariate correlations showed that greater drive for muscularity was significantly correlated with most of the measures and their subscales. However, in a multiple regression analysis, the only significant predictor of drive for muscularity was support for group-based dominance hierarchies (Adj. R(2)=.17). These results suggest that men's drive for muscularity is associated with a socio-political ideology that favours social dominance.

Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee. PMID:21078917

In neurodegenerative disorders effective treatments are urgently needed, along with methods to detect that the treatment worked. In this review we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is a caused by loss of the Survival Motor Neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving towards clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression. PMID:23939659

Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings

On the basis of observational studies, child health practitioners in primary care settings should consider the diagnosis of congenital muscular torticollis (CMT)in infants with risk factors from birth history for intrauterine malpositioning or constraint (C). On the basis of observational studies, CMT is often associated with other conditions, including positional plagiocephaly and gross motor delays from weakened truncal muscles and/or lack of head control in early infancy (C). On the basis of observational studies, child health practitioners should counsel parents that infants should be on their stomachs frequently whenever they are awake and under direct adult supervision to develop their prone motor skills (C). On the basis of consensus, early identification of CMT(with or without positional plagiocephaly) and prompt referral to a physical therapist experienced in the treatment of CMT should be considered to avoid more costly or invasive treatments, such as cranial orthoses or surgery (D).

LGMD refers to a class of muscular dystrophies with onset in the proximal muscles. They are genetically heterogeneous, with both autosomal recessive and dominant forms. The autosomal recessive forms are more common and in general follow a more severe course compared to the dominant forms. It is important to reach a specific genetic diagnosis beyond making a group diagnosis of LGMD to provide adequate genetic counseling, to predict risks for the patient such as the development of cardiomyopathy, and to be able to take advantage of specific treatments when they become available. Establishing a specific diagnosis requires knowledge about the individual clinical features, expert analysis of the muscule biopsy, and the guided initiation of appropriate genetic testing.

Hypercholesterolemia is a major risk factor for cardiovascular diseases. The 2012-2013 survey of Canada's public health measures revealed that dyslipidemia was present in 38% of the respondents aged between 18 and 79 years. According to the American College of Cardiology, the American Heart Association, the Canadian Cardiovascular Society and the Canadian Working Group Consensus, statins remain the treatment of choice for dyslipidemia and the reduction of cardiovascular risk. However, concerns and questions persist regarding statins use and safety, potential and harmful muscular side-effects, interactions with exercise, and molecular mechanisms of myotoxicity. The goal of the present review is to provide a clear picture of the clinical situation and to investigate possible mechanisms of statin-induced myopathy. A better understanding of muscle pathology in statin users is absolutely essential to minimize their muscle symptoms and to provide a sound clinical basis for the management of cardiovascular risk.

Cardiac involvement (CI) in form of myocardial thickening in a patient with genetically confirmed facioscapulohumeral muscular dystrophy (FSHMD) has not been reported. The patient is a 50-year-old male with a tandem repeat size of 17 and 14 kb in the D4Z4 locus on chromosome 4q35. The clinical cardiologic investigation was normal. Blood pressure was 150/90 mm Hg. Funduscopy, 24-hour ambulatory ECG, and 24-hour blood pressure monitoring were normal. ECG showed incomplete right bundle branch block, ST elevation in V2-V4, tall T waves in V3-V5, and hypertrophy signs. Echocardiography revealed left ventricular myocardial thickening of the posterior wall (11.7 mm) and the septum (15.5 mm). In conclusion, CI in genetically confirmed FSHMD may manifest not only as ECG abnormalities but also as left ventricular myocardial thickening. Copyright 2005 S. Karger AG, Basel.

Insufficient serum levels of 25-hydroxyvitamin D [25(OH)D] is a risk factor for osteoporosis. A new paradigm is emerging with the locally synthesized 1,25(OH)2D within osteoblasts and osteoclasts as the essential pathway for the effects of 25(OH)D in regulating bone remodeling via direct or indirect activation of the specific receptor VDR. Vitamin D has positive effects on fracture risk, muscular function and risk of falls; these effects are observed when serum levels of 25(OH)D are above 30 ng/ml (75 nmol/l). Vitamin D dosing interval may be relevant for reducing the risk of fracture, with evidence suggesting positive effects with short intervals of 3 months or less. It is recommended to maintain an optimal serum level of 25(OH)D when managing patients with osteoporosis or at risk of this bone disease.

During the last decade rapid development has occurred in defining nuclear gene mutations causing mitochondrial disease. Some of these newly defined gene mutations cause neonatal or early infantile onset of disease, often associated with severe progressive encephalomyopathy combined with other multi-organ involvement such as cardiomyopathy or hepatopathy and with early death. Findings suggesting myopathy in neonates are hypotonia, muscle weakness and wasting, and arthrogryposis. We aim to describe the clinical findings of patients with mitochondrial disease presenting with muscular manifestations in the neonatal period or in early infancy and in whom the genetic defect has been characterized. The majority of patients with neonatal onset of mitochondrial disease have mutations in nuclear genes causing dysfunction of the mitochondrial respiratory chain, leading to defective oxidative phosphorylation.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by muscle atrophy and weakness due to degeneration of the anterior horn cells in the spinal cord. A great need exists for an effective treatment of SMA, a disease that often causes severe disability in patients who are cognitively intact and can have a normal life expectancy. Unlike many other neurologic diseases, SMA can be easily diagnosed through genetic testing. Also, preclinical progress over the last 2 decades has been major, with the discovery of the gene and of a "druggable" modifying gene that provides one of several promising targets for treatment. SMA is rare but is a common orphan disease, so trials should be feasible, raising the hope that we will find effective treatments for this disorder.

Physical fitness is one of the strongest predictors of individual future health status. Together with cardiorespiratory fitness (CRF), muscular strength has been increasingly recognized in the pathogenesis and prevention of chronic disease. We review the most recent literature on the effect of muscular strength in the development of cardiovascular disease, with special interest in elucidating its specific benefits beyond those from CRF and body composition. Muscular strength has shown an independent protective effect on all-cause and cancer mortality in healthy middle-aged men, as well as in men with hypertension and patients with heart failure. It has also been inversely associated with age-related weight and adiposity gains, risk of hypertension, and prevalence and incidence of the metabolic syndrome. In children and adolescents, higher levels of muscular fitness have been inversely associated with insulin resistance, clustered cardiometabolic risk, and inflammatory proteins. Generally, the influence of muscular fitness was weakened but remained protective after considering CRF. Also, interestingly, higher levels of muscular fitness seems to some extent counteract the adverse cardiovascular profile of overweight and obese individuals. As many of the investigations have been conducted with non-Hispanic white men, it is important to examine how race/ethnicity and gender may affect these relationships. To conclude, most important effects of resistance training are also summarized, to better understand how higher levels of muscular fitness may result in a better cardiovascular prognosis and survival.

This study analyses the changes in the electromyographic activity (EMG) of six major muscles of the leg during an incremental running test carried out on a treadmill. These muscles, the gluteus maximus (GM), biceps femoris (BF), vastus lateralis (VL), rectus femoris (RF), tibialis anterior (TA) and gastrocnemius (Ga) are known to have quite different functions during running. The aim of this study was to develop a methodology adapted to the analysis of integrated EMG (iEMG) running results, and to test the chronology of the onset of fatigue of the major muscles involved in running. Nine well-trained subjects [VO(2max) 76 (2.9) ml.min(-1).kg(-1)] took part in this study. They completed a running protocol consisting of 4 min stages, incrementally increasing in speed until exhaustion. The EMG signal was recorded during ten bursts of activation analysed separately at 45 s and 3 min 40 s of each stage. During running, consideration of the alteration in stride frequency with either an increase in speed or the onset of fatigue appears to be an indispensable part of the assessment of muscular fatigue. This allows the comparison of muscular activation between the various stage speeds by the use of common working units. Distance seems to be the only working unit that allows this comparison and thus the determination of the appearance of fatigue during running. The biarticular hip-mobilising muscles (RF and BF), which present two different bursts of activation during one running cycle, are the muscles that show the earliest signs of fatigue.

This study aimed to investigate how the trunk muscularity is related to sprint running performance. In 23 youth soccer players, the cross-sectional images at the mid level of each of L1-L2, L2-L3, L3-L4, L4-L5, and L5-S1 were obtained using magnetic resonance imaging to determine the cross-sectional areas (CSAs) of rectus abdominis, oblique, psoas major, quadratus lumborum and erector spinae muscles. The times taken to sprint over 20 m were measured, and the mean velocity of running was calculated for each of the 2 distances (V (10 m) and V (20 m)) and for the distance from 10 m to 20 m (V (10-20 m)). The CSA values of the 5 slice levels for all muscles except for the quadratus lumborum and those of the 3 slice levels (L1-L2, L2-L3 and L3-L4) for the quadratus lumborum were averaged and expressed relative to the two-third power of body mass (CSA/BM (2/3)). The CSA/BM (2/3) values of the erector spinae and quadratus lumborum were selected as significant contributors to predict V (10 m) ( R(2)=0.450), V (20 m) ( R(2)=0.504) and V (10-20 m) ( R(2)=0.420). The current results indicate that the muscularity of the erector spinae and quadratus lumborum contributes to achieving a high performance in sprint running over distances of less than 20 m.

Mutations in the DMD gene result in Duchenne or Becker muscular dystrophy due to absent or altered expression of the dystrophin protein. The more severe Duchenne muscular dystrophy typically presents around ages 2 to 5 with gait disturbance, and historically has led to the loss of ambulation by age 12. It is important for the practicing pediatrician, however, to be aware of other presenting signs, such as delayed motor or cognitive milestones, or elevated serum transaminases. Becker muscular dystrophy is milder, often presenting after age 5, with ambulation frequently preserved past 20 years and sometimes into late decades.

Surgical correction of the congenital muscular torticollis (CMT) is recommended for patients with unsuccessful conservative treatment. The aim of this study is to evaluate the efficacy of surgical release of congenital muscular torticollis in neglected cases. We retrospectively evaluated the data of our patients in terms of age, sex, clinical presentation, localization of the lesion, diagnostic tests, and additional abnormalities. The age at operation ranged from 6 to 23 years. Complete muscular release as determined by pre-operative and postoperative range of motion measurements was achieved in all of the patients by bipolar release. In this study, neck motion and head tilt showed marked improvement with surgical treatment in cases with CMT who were admitted to the hospital lately. Congenital muscular torticollis patients can benefit from surgical intervention above the age of 5. Bipolar release is an adequate and complication-free method.

Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy. PMID:17785520

effect a and (3 can be taken as velocity functions. REFERENCE [1] R. J. PODOLSKY, "The chemical thermodynamics and molecular mechanism of muscular contraction," Ann. New York Acad. Sci., Vol. 72 (1959), pp. 522-537.

Communicating about Duchenne muscular dystrophy and its prognosis can be difficult for affected children and their family. We focused on how physicians provide support to the mothers of children with Duchenne muscular dystrophy who have difficulty communicating about the condition with their child. The eligible participants were certified child neurologists of the Japanese Society of Child Neurology. Participants responded to questionnaires consisting of free descriptions of a vignette of a child with Duchenne muscular dystrophy and a mother. We analyzed 263 responses of the participants. We found 4 themes on advising mothers, involving encouraging communication, family autonomy, supporting family, and considering the child's concerns. These results provide a better understanding of the communication between physicians and family members who need help sharing information with a child with Duchenne muscular dystrophy. These findings will assist clinical practitioners in supporting families and the affected children throughout the course of their illness.

Muscular dystrophies are heritable and heterogeneous neuromuscular disorders characterized by the primary wasting of skeletal muscle, usually caused by mutations in the proteins forming the link between the cytoskeleton and the basal lamina. As a result of mutations in the dystrophin gene, Duchenne muscular dystrophy patients suffer from progressive muscle atrophy and an exhaustion of muscular regenerative capacity. No efficient therapies are available. The evidence that adult stem cells were capable of participating in the regeneration of more than their resident organ led to the development of potential stem cell treatments for degenerative disorder. In the present review, we describe the different types of myogenic stem cells and their possible use for the progression of cell therapy in Duchenne muscular dystrophy.

The study investigated the effects of low-intensity exercise on muscular fitness when combined with vascular occlusion. Nineteen college male and female students performed two sets of a 5-min step exercise using a 12-inch bench three times per week for 5 weeks. During the step exercise, blood flow to one leg was restricted (vascular occlusion) with a blood pressure cuff, while the other leg was not occluded. Muscular strength of the occluded leg was significantly increased over the nonoccluded leg (p < 0. 05). Muscular endurance and muscle mass were improved after 5 weeks of training (p < 0.05); however, the changes between the two legs were not significantly different (p > 0.05). Exercise with vascular occlusion has the potential to be an alternative form of training to promote muscular strength.

Spinal muscular atrophy is one of the most heterogeneous of the single-gene neuromuscular disorders. The broad spectrum of severity, with onset from the prenatal period to adulthood, presents unique challenges in the design and implementation of clinical trials. The clinical classification of subjects into severe (type 1), intermediate (type 2), and mild (type 3) subtypes has proved useful both in enhancing communication among clinicians internationally and in forging the collaborative development of outcome measures for clinical trials. Ideally, clinical trial design in spinal muscular atrophy must take into account the spinal muscular atrophy type, patient age, severity-of-affection status, nature of the therapeutic approach, timing of the proposed intervention relative to disease progression, and relative homogeneity of the cohort to be studied. Following is an overview of the challenges and opportunities, current and future therapeutic strategies, and progress to date in clinical trials in spinal muscular atrophy. PMID:17761650

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Muscular dystrophies are genetic conditions leading to muscle degeneration and often, impaired regeneration. Duchenne Muscular Dystrophy is a prototypical form of muscular dystrophy, and like other forms of genetically inherited muscle diseases, pathological progression is variable. Variability in muscular dystrophy can arise from differences in the manner in which the primary mutation impacts the affected protein's function; however, clinical heterogeneity also derives from secondary mutations in other genes that can enhance or reduce pathogenic features of disease. These genes, called genetic modifiers, regulate the pathophysiological context of dystrophic degeneration and regeneration. Understanding the mechanistic links between genetic modifiers and dystrophic progression sheds light on pathologic remodeling, and provides novel avenues to therapeutically intervene to reduce muscle degeneration. Based on targeted genetic approaches and unbiased genomewide screens, several modifiers have been identified for muscular dystrophy, including extracellular agonists of signaling cascades. This review will focus on identification and possible mechanisms of recently identified modifiers for muscular dystrophy, including osteopontin, latent TGFβ binding protein 4 (LTBP4) and Jagged1. Moreover, we will review the investigational approaches that aim to target modifier pathways and thereby counteract dystrophic muscle wasting.

The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients.

Introduction Cardiac involvement is a common feature in muscular dystrophies. It presents as heart failure and/or arrhythmia. Traditionally, dystrophic cardiomyopathy is treated with symptom-relieving medications. Identification of disease-causing genes and investigation on pathogenic mechanisms have opened new opportunities to treat dystrophic cardiomyopathy with gene therapy. Replacing/repairing the mutated gene and/or targeting the pathogenic process/mechanisms using alternative genes may attenuate heart disease in muscular dystrophies. Areas covered Duchenne muscular dystrophy is the most common muscular dystrophy. Duchenne cardiomyopathy has been the primary focus of ongoing dystrophic cardiomyopathy gene therapy studies. Here, we use Duchenne cardiomyopathy gene therapy to showcase recent developments and to outline the path forward. We also discuss gene therapy status for cardiomyopathy associated with limb-girdle and congenital muscular dystrophies, and myotonic dystrophy. Expert opinion Gene therapy for dystrophic cardiomyopathy has taken a slow but steady path forward. Preclinical studies over the last decades have addressed many fundamental questions. Adeno-associated virus-mediated gene therapy has significantly improved the outcomes in rodent models of Duchenne and limb girdle muscular dystrophies. Validation of these encouraging results in large animal models will pave the way to future human trials. PMID:27340611

Background The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Methods Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. Findings The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients. PMID:26029630

The aim of this study was primarily to determine the reliability and factor validity of four muscular endurance tests, and secondly, to identify gender differences in muscular endurance tests. For this purpose, a new muscular endurance test was constructed for pupils aged between seven and eight (CROCO). The research was done on a sample of 71 pupils aged between seven and eight (35 girls and 36 boys), their body height being 129.2 +/- 1.3 cm for boys and 127.1 +/- 1.4 cm for girls, body weight 29.3 +/- 7.2 kg for boys and 27.1 +/- 6.5 for girls. According to the results, all tests have shown a good level of reliability and factor validity. Also, the present study confirmed the expected gender differences (p < or = 0.05). In all muscular endurance tests, the boys were slightly better than girls (p < or = 0.05). The authors recommend the implementation of the CROCO test and other muscular endurance tests used in this study, both for the implementation in the primary school curricula and in sports because of these tests' satisfactory level of reliability and factor validity. The school curricula need to be adjusted to the age and gender differences of children in order to promote positive health behavior from the earliest age on the one hand, and on the other to be able to objectively measure muscular endurance.

To compare the different techniques used by paramedics in handling an emergency evacuation chair and to identify themore ergonomically favourable technique, based on an analysis ofmuscular activity using surface electromyography. The trial was based on descending stairs, through four possible arrangements for the same transport operation, where the study variables were: worker anthropometrics (5th and 95th percentiles, corresponding to the extremes of the normal height-weight distribution curve), worker location during chair transport (upper or lower end of the chair), and the position of the individual at the lower end (facing front or backwards during descent). For both workers participating in the study, the more favourable working position during chair descent was at the lower end of the chairwhile facing forward, as this was associated with less muscular activity. In general, physical demands on the various muscles studied was greater for the worker corresponding to the 5th percentile (i.e., lower height-weight), except for the paravertebral musculature which, for certain maneuvers involving manipulation was significantly greater than the 95th percentile. When descending stairs while transporting an emergency evacuation chair, the position involving least muscular activity is located at the lower end of the chair, and descending while facing forwards. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

Fukuyama-type congenital muscular dystrophy (FCMD) and laminin-alpha2 deficient congenital muscular dystrophy (MDC1A) are congenital muscular dystrophies (CMDs) and they both are categorized into the same clinical entity of muscular dystrophy as Duchenne muscular dystrophy (DMD). All three disorders share a common etiologic defect in the dystrophin-glycoprotein complex, which connects muscle structural proteins with the extracellular basement membrane. To investigate the pathophysiology of these CMDs, we generated microarray gene expression profiles of skeletal muscle from patients in various clinical stages. Despite diverse pathological changes, the correlation coefficient of overall gene expression among these samples was considerably high. We performed a multi-dimensional statistical analysis, the Distillation, to extract determinant genes that distinguish CMD muscle from normal controls. Up-regulated genes were primarily extracellular matrix (ECM) components, whereas down-regulated genes included structural components of mature muscle. These observations reflect active interstitial fibrosis with less active regeneration of muscle cell components in the CMDs, characteristics that are clearly distinct from those of DMD. Although the severity of fibrosis varied among the specimens tested, ECM gene expression was consistently high without substantial changes through the clinical course. Further, in situ hybridization showed more prominent ECM gene expression on muscle cells than on interstitial tissue cells, suggesting that ECM components are induced by regeneration process rather than by 'dystrophy.' These data imply that the etiology of FCMD and MDC1A differs from that of the chronic phase of classical muscular dystrophy, and the major pathophysiologic change in CMDs might instead result from primary active fibrosis.

The aim of the present study was to test the hypothesis that performance in throwing events is associated with muscular characteristics of both upper and lower limbs. Thirty-eight male throwers volunteered to participate. Bench press and half squat tests were conducted on a guided barbell. The barbell displacement signal was recorded using a kinematic system. Maximal power, corresponding optimal velocity and force (P(max)S, V(opt)S, F(opt)S and P(max)BP, V(opt)BP, F(opt)BP for half squat and bench press, respectively) were extrapolated from the power-velocity relationship. Lower limb stiffness (K) was determined during maximal hopping. The results demonstrated that P(max)S and P(max)BP were correlated with each thrower's season's best performance (SBP, R=0.54, P<0.01 and R=0.71, P<0.001, respectively). P(max)S expressed relative to body mass was not correlated with SBP. K was significantly correlated with SBP (R=0.66, P<0.001). The relationship between P (max)BP expressed relative to body mass and SBP remained significant ( R=0.54, P<0.001). The results of the study suggest that high strength and stiffness values for lower limbs and strength and velocity characteristics for upper limbs may be associated with athletic throwing performance.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by progressive muscle weakness. The disease locus maps to 4q35 and is associated with a de novo DNA rearrangement, detected by a probe p13E-11 (D4F104S1) which maps proximal to the disease locus. An informative distal flanking marker for this condition is still required. Using p13E-11, we have analyzed 35 FSHD families in which the disease is apparently associated with a new mutation. Twenty three of these cases were found to have a smaller rearranged DNA fragment which was not present in either of the parents. Pulsed-field gel analysis of 5 of these families also revealed evidence of DNA deletion. During the course of this study, we identified one case with a DNA rearrangement which was also present in the unaffected mother, but at very low intensity. This finding has been confirmed by pulsed-field gel analysis, and indicates that the mother is probably a gonosomal mosaic. In order to saturate the FSHD region with new DNA markers, a laser microdissection and microcloning technique was used to construct a genomic library from the distal end of chromosome 4. Of the 72 microclones analyzed, 42 mapped into the relevant 4q35 region. 4 sequences were conserved and may be considered potential candidate genes for FSHD. The microclones mapping to 4q35 are under study to identify additional polymorphic markers for the FSHD region.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

Objectives: The objectives of this study were to develop a conceptual model of quality of life (QOL) in muscular dystrophies (MDs) and review existing QOL measures for use in the MD population. Methods: Our model for QOL among individuals with MD was developed based on a modified Delphi process, literature review, and input from patients and patient advocacy organizations. Scales that have been used to measure QOL among patients with MD were identified through a literature review and evaluated using the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) checklist. Results: The Comprehensive Model of QOL in MD (CMQM) captures 3 broad domains of QOL (physical, psychological, and social), includes factors influencing self-reported QOL (disease-related factors, support/resources, and expectations/aspirations), and places these concepts within the context of the life course. The literature review identified 15 QOL scales (9 adult and 6 pediatric) that have been applied to patients with MD. Very few studies reported reliability data, and none included data on responsiveness of the measures to change in disease progression, a necessary psychometric property for measures included in treatment and intervention studies. No scales captured all QOL domains identified in the CMQM model. Conclusions: Additional scale development research is needed to enhance assessment of QOL for individuals with MD. Item banking and computerized adaptive assessment would be particularly beneficial by allowing the scale to be tailored to each individual, thereby minimizing respondent burden. PMID:25663223

Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds. The ventricular folds contained anteriorly coursing thyroarytenoid and ventricularis muscle fibers that were in the lower half of the ventricular fold posteriorly, and some ventricularis muscle was evident in the upper and lateral portions of the fold more anteriorly. Very little muscle tissue was observed in the medial half of the fold, and the anterior half of the ventricular fold was largely devoid of any muscle tissue. All 4 larynges contained muscle bundles that coursed superiorly and medially through the upper half of the fold, toward the lateral margin of the epiglottis. Although variability of expression was evident, a well-defined thyroarytenoid muscle was readily apparent lateral to the arytenoid cartilage in all specimens.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA. PMID:26124831

Introduction Duchenne muscular dystrophy (DMD) is a relatively common inherited disorder caused by defective expression of the protein dystrophin. The most direct approach to treating this disease would be to restore dystrophin production in muscle. Recent progress has greatly increased the prospects for successful gene therapy of DMD, and here we summarize the most promising developments. Areas Covered Gene transfer using vectors derived from adeno-associated virus (AAV) has emerged as a promising method to restore dystrophin production in muscles bodywide, and represents a treatment option applicable to all DMD patients. Using information gleaned from PubMed searches of the literature, attendance at scientific conferences and results from our own lab, we provide an overview of the potential for gene therapy of DMD using AAV vectors including a summary of promising developments and issues that need to be resolved prior to large-scale therapeutic implementation. Expert Opinion Of the many approaches being pursued to treat DMD and BMD, gene therapy based on AAV-mediated delivery of microdystrophin is the most direct and promising method to treat the cause of the disorder. The major challenges to this approach are ensuring that microdystrophin can be delivered safely and efficiently without eliciting an immune response. PMID:26594599

Duchenne Muscular Dystrophy (DMD) is an X-linked inherited neuromuscular disorder caused by mutations in the dystrophin gene (DMD; locus Xp21.2). The mutation spectrum of DMD is unique in that 65% of causative mutations are intragenic deletions, with intragenic duplications and point mutations (along with other sequence variants) accounting for 6% to 10% and 30% to 35%, respectively. The strategy for molecular diagnostic testing for DMD involves initial screening for deletions/duplications using microarray-based comparative genomic hybridization (array-CGH) followed by full-sequence analysis of DMD for sequence variants. Recently, next-generation sequencing (NGS)-based targeted gene analysis has become clinically available for detection of point mutations and other sequence variants (small insertions, deletions, and indels). This unit initially discusses the strategic algorithm for establishing a molecular diagnosis of DMD and later provides detailed protocols of current molecular diagnostic methods for DMD, including array-CGH, PCR-based Sanger sequencing, and NGS-based sequencing assay.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the gene CAPN3 located in the chromosome region 15q15.1-q21.1. To date more than 300 mutations have been described. This gene encodes for a 94-kDa nonlysosomal calcium-dependent cysteine protease and its function in skeletal muscle is not fully understood. It seems that calpain-3 has an unusual zymogenic activation that involves, among other substrates, cytoskeletal proteins. Calpain-3 is thought to interact with titin and dysferlin. Calpain-3 deficiency produces abnormal sarcomeres that lead eventually to muscle fiber death. Hip adductors and gluteus maximus are the earliest clinically affected muscles. No clinical differences have been reported depending on the type of mutation in the CAPN3 gene. The muscle biopsy shows variability of fiber size, interstitial fibrosis, internal nuclei, lobulated fibers, and, in some cases, presence of eosinophils. Recent gene expression profiling studies have shown upregulation of interleukin-32 and immunoglobulin genes, which may explain the eosinophilic infiltration. Two mouse knockout models of CAPN3 have been characterized. There are no curative treatments for this disease. However, experimental therapeutics using mouse models conclude that adeno-associated virus (AAV) vectors seem to be one of the best approaches because of their efficiency and persistency of gene transfer.

Lipomatous myopathy is a degenerative muscle pathology characterized by the substitution of muscle cells with adipose tissue, sporadically reported in cattle, pigs, and rarely in sheep, horses and dogs. This study investigated the pathology of this myopathy in 40 muscle samples collected from regularly slaughtered Piedmontese cattle living in Piedmont region (Italy). None of the animals showed clinical signs of muscular disease. Muscle specimens were submitted to histological and enzymatic investigations. Gross pathology revealed a different grade of infiltration of adipose tissue, involving multiple or single muscles. The most affected regions were the ventral abdomen and the shoulders, especially the cutaneous muscles and the muscles of the thoracic group. Morphological staining revealed an infiltration of adipose tissue varying in distribution and severity, changes in muscle fibre size and increased number of fibres with centrally located nuclei, suggesting muscle degeneration-regeneration. Necrosis and non-suppurative inflammatory cells were also seen. Furthermore, proliferation of connective tissue and non-specific myopathic changes were present. Chemical and physical characteristics of the affected tissue were also evaluated. The authors discuss about the aetiopathogenesis and classification of this muscle disorder whose histological lesions were similar to those reported in human dystrophies.

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. Heart failure is a classical complication in this disease. Little data are available about systolic dyssynchrony in DMD. We sought to assess the prevalence of left ventricular dysfunction and systolic asynchrony in DMD patients using echocardiographic parameters. We performed electrocardiography and echocardiography for adult's patients with DMD. For systolic dyssynchrony assessment, echocardiography-Doppler was performed and completed by tissular Doppler imaging. 48 DMD were included in our study. Age ranged from 20 to 37 years. QRS duration >120 ms was present in 10 patients/48 and 1 patient disclosed a QRS duration >150 ms. Left ventricular (LV) ejection fraction (EF) ranged from 10 to 62 % with a median of 43 %. Inter-ventricular asynchrony was found in 11.9 % of patients with EF 35 %. Intra-ventricular asynchrony was present in 6 % of patients with EF

Despite an expansive wealth of research following the discovery of the DMD gene 25 years ago, there is still no curative treatment for Duchenne muscular dystrophy. However, there are currently many promising lines of research, including cell-based therapies and pharmacological reagents to upregulate dystrophin via readthrough of nonsense mutations or by upregulation of the dystrophin homolog utrophin. Here we review genetic-based therapeutic strategies aimed at the amelioration of the DMD phenotype. These include the reintroduction of a copy of the DMD gene into an affected tissue by means of a viral vector; correction of the mutated DMD transcript by antisense oligonucleotide-induced exon skipping to restore the open reading frame; and direct modification of the DMD gene at a chromosomal level through genome editing. All these approaches are discussed in terms of the more recent advances, and the hurdles to be overcome if a comprehensive and effective treatment for DMD is to be found. These hurdles include the need to target all musculature of the body. Therefore any potential treatment would need to be administered systemically. In addition, any treatment needs to have a long-term effect, with the possibility of readministration, while avoiding any potentially detrimental immune response to the vector or transgene.

Spinal muscular atrophy (SMA), a potentially devastating disease marked by progressive weakness and muscle atrophy resulting from the dysfunction and loss of motor neurons of the spinal cord, has emerged in recent years as an attractive target for therapeutic intervention. Caused by a homozygous mutation to the Survival of Motor Neurons 1 (SMN1) gene on chromosome 5q, the severity of the clinical phenotype in SMA is modulated by the function of a related protein, Survival of Motor Neurons 2 (SMN2). SMN2 predominantly produces an unstable SMN transcript lacking exon 7; only about 10% of the transcription product produces a full-length, functional SMN protein. Several therapeutic strategies have targeted this gene with the goal of producing increased full-length SMN transcript, thereby modifying the underlying mechanism. Drugs that have increased SMN2 function, in vitro, are now explored for potential therapeutic benefit in this disease. Alternative approaches, including neuroprotective, muscle anabolic, gene and cell replacement strategies, also hold promise. The recent advances in preclinical research and the development of a wider range of animal models for SMA continue to provide cautious optimism that effective treatments for SMA will eventually emerge. PMID:21179609

This article reviews clinical, genetic, and therapeutic advances in spinal muscular atrophies (SMAs), inherited disorders characterized by motor neuron loss and muscle weakness. There has been progress in defining the clinical and genetic features of at least 16 distinct forms of SMA. The genes associated with 14 of these disorders have been identified in the last decade, including four within the last year: TRPV4, ATP7A, VRK1, and HSPB3. Genetic testing is now available for many SMAs, providing important diagnostic and prognostic information. Cell and animal models of SMAs have been used to further understand how mutations in SMA-associated genes, which code for proteins involved in diverse functions such as transcriptional regulation, RNA processing, and cytoskeletal dynamics, lead to motor neuron dysfunction and loss. In the last year, there has also been remarkable progress in preclinical therapeutics development for proximal SMA using gene therapy, antisense oligonucleotides, and small molecules. The advances in the clinical and genetic characterization of different forms of SMAs have important implications for clinical evaluation and management of patients. The identification of multiple, novel SMA-causing genes will lead to an improved understanding of motor neuron disease biology and may provide novel targets for therapeutics development.

The motor neuron disease spinal muscular atrophy (SMA) is one of the leading genetic killers of infants worldwide. SMA is caused by mutation of the survival motor neuron 1 (SMN1) gene and deficiency of the survival motor neuron (SMN) protein. All patients retain one or more copies of the SMN2 gene, which (by producing a small amount of the SMN protein) rescues embryonic lethality and modifies disease severity. Rapid progress continues in dissecting the cellular functions of the SMN protein, but the mechanisms linking SMN deficiency with dysfunction and loss of functioning motor units remain poorly defined. Clinically, SMA should to be distinguished from other neuromuscular disorders, and the diagnosis can be readily confirmed with genetic testing. Quality of life and survival of SMA patients are improved with aggressive supportive care including optimized respiratory and nutritional care and management of scoliosis and contractures. Because SMA is caused by inadequate amounts of SMN protein, one aim of current SMA therapeutics development is to increase SMN protein levels in SMA patients by activating SMN2 gene expression and/or increasing levels of full-length SMN2 transcripts. Several potential therapeutic compounds are currently being studied in clinical trials in SMA patients.

Recent studies have indicated that muscular disorders may be of importance for the development of increased pain sensitivity in patients with chronic tension-type headache. The objective of the present study was to investigate this hypothesis by examining the pain perception in tension-type headache with and without muscular disorders defined as increased tenderness. We examined 28 patients with episodic tension-type headache, 28 patients with chronic tension-type headache, and 30 healthy controls. Pericranial myofascial tenderness was recorded with manual palpation, and pressure pain detection and tolerances in cephalic and extracephalic locations with an electronic pressure algometer. In addition, thermal pain sensitivity and electromyographic activity were recorded. The main result was significantly lower pressure pain detection thresholds and tolerances in all the examined locations in patients with chronic tension-type headache with a muscular disorder compared to those without a muscular disorder. There were no such differences in any of the examined locations when the two subgroups of patients with episodic tension-type headache were compared. Thermal pain sensitivity did not differ between patients with and without a muscular disorder, while electromyographic activity levels were significantly higher in patients with chronic tension-type headache with than in those without a muscular disorder. Our results strongly indicate that prolonged nociceptive stimuli from the pericranial myofascial tissue sensitize the central nervous system and, thereby, lead to an increased general pain sensitivity. Muscular factors may, therefore, be of major importance for the conversion of episodic into chronic tension-type headache. The present study complements the understanding of the important interactions between peripheral and central factors in tension-type headache and may lead to a better prevention and treatment of the most prevalent type of headache.

Spinal Muscular Atrophy (SMA), a recessive hereditary neurodegenerative disease in humans, has been linked to mutations in the survival motor neuron (SMN) gene. SMA patients display early onset lethality coupled with motor neuron loss and skeletal muscle atrophy. We used Drosophila, which encodes a single SMN ortholog, survival motor neuron (Smn), to model SMA, since reduction of Smn function leads to defects that mimic the SMA pathology in humans. Here we show that a normal neuromuscular junction (NMJ) structure depends on SMN expression and that SMN concentrates in the post-synaptic NMJ regions. We conducted a screen for genetic modifiers of an Smn phenotype using the Exelixis collection of transposon-induced mutations, which affects approximately 50% of the Drosophila genome. This screen resulted in the recovery of 27 modifiers, thereby expanding the genetic circuitry of Smn to include several genes not previously known to be associated with this locus. Among the identified modifiers was wishful thinking (wit), a type II BMP receptor, which was shown to alter the Smn NMJ phenotype. Further characterization of two additional members of the BMP signaling pathway, Mothers against dpp (Mad) and Daughters against dpp (Dad), also modify the Smn NMJ phenotype. The NMJ defects caused by loss of Smn function can be ameliorated by increasing BMP signals, suggesting that increased BMP activity in SMA patients may help to alleviate symptoms of the disease. These results confirm that our genetic approach is likely to identify bona fide modulators of SMN activity, especially regarding its role at the neuromuscular junction, and as a consequence, may identify putative SMA therapeutic targets. PMID:18791638

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron (SMN1) gene, affecting approximately 1 in 10,000 live births. Even though a specific therapy for SMA is not currently available, a newborn screening test may allow the child to be enrolled in a clinical trial before irreversible neuronal loss occurs and enable patients to obtain more proactive treatments. Until an effective treatment is found to cure or arrest the progression of the disease, prevention of new cases through carrier detection and prenatal diagnosis becomes extremely important. The correlation between the SMA phenotype and the SMN2 copy number and the demonstration that sufficient SMN protein from SMN2 in transgenic mice can ameliorate the disease has made the SMN2 gene an obvious target that is being modulated in current therapeutic trials. Most recent work, utilizing gene therapy, has also shown a rescue of the phenotype in the mouse model. Since SMA children are often asymptomatic at birth, newborn screening is a means which will allow the implementation of the most early intervention to take place, before the irreversible loss of motor neurons. Since there is no effective cure for SMA presently, prevention through the identification of carriers becomes an important alternative and has recently been initiated. Treatment and prevention of SMA are complementary responses to the scourge presented by SMA. This review first describes the molecular genetics of SMA and then focuses on newborn screening, as a means of ensuring the earliest intervention, and the prevention through population carrier screening.

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder characterized by progressive muscle wasting. DMD is a fatal X-linked recessive disorder with an estimated prevalence of 1 in 3,500 male live births. This disease has long been associated with intellectual impairment. Research has shown that boys with DMD have variable intellectual performance, indicating the presence of specific cognitive deficits. The aim of the study was to use a battery of intelligence, learning, and memory tests to identify a neuropsychological profile in boys with DMD. A total of 22 boys diagnosed with DMD in the age range of 6 to 10 years old were evaluated using the Wechsler Intelligence Scale for Children-Third Edition, Rey's Auditory Verbal Learning Test, and the Memory for Designs Test. The data were interpreted using means, standard deviations, percentages, and percentiles. Normative data were also used for further interpretation. The results showed that boys with DMD had a significantly lower IQ (88.5). Verbal IQ (86.59) was found to be lower than Performance IQ (92.64). There was evidence of impaired performance on the Processing Speed, Freedom From Distractibility, and Verbal Comprehension Indexes. Specific deficits in information processing, complex attention, immediate verbal memory span, verbal working memory, verbal comprehension, vocabulary, visuoconstruction ability, and verbal learning and encoding were observed. However, perceptional organization, general fund of information, abstract reasoning, visual discrimination and acuity, visual learning and memory, and verbal memory were adequate. The neuropsychological findings support the hypothesis that these children have specific cognitive deficits as opposed to a global intellectual deficit.

Spinal muscular atrophy (SMA) causes respiratory compromise that is difficult to assess in young children. The forced oscillation technique (FOT) is commercially available for children as young as 2 years of age and is nonvolitional. The aim of this study was to assess the usefulness of FOT in young children with SMA. Children with SMA aged < 10 years were recruited. FOT was performed every 3 months for 12 months (five visits). Spirometry and assisted and unassisted peak cough flow (PCF) were performed where possible. Polysomnography was performed on children with type 2 SMA. Clinical information included SMA type, chest infections, Cobb angle, medications, and mobility. Regression analysis assessed relationships between FOT and FVC, PCF, and apnea/hypopnea index (AHI). Analysis of variance sought relationships to clinical characteristics. Twelve children (seven male) were recruited; mean age was 6.26 (± 2.59) years. Respiratory reactance at 8 Hz (Xrs8) (mean z score, +1.41; SD, 1.90; P < .03) and respiratory resistance at 8 Hz (Rrs8) (mean z score, +0.66; SD, 1.34; P = .12) were abnormal. Four children performed spirometry. Linear relationships to Xrs8 exist: FVC (R2, 0.54), unassisted PCF (R2, 0.33), assisted PCF (R2, 0.43), and AHI (R2, 0.32). Over 12 months, Xrs8z score worsened (rate of change of +1.08, P < .001) and Rrs8z score worsened (rate of change +0.51, P < .001). No relationship (P > .05) was found between clinical characteristics and FOT values. FOT is feasible in young children with SMA, with abnormal values of reactance and resistance on grouped data, worsening over 12 months. Xrs8 is related to respiratory tests used to monitor progress in SMA (FVC, PCF, AHI). Further research on the value of FOT in managing individuals is warranted.

Objective: The objective of this study was to estimate the total cost of illness and economic burden of Duchenne muscular dystrophy (DMD). Methods: Patients with DMD from Germany, Italy, United Kingdom, and United States were identified through Translational Research in Europe–Assessment & Treatment of Neuromuscular Diseases registries and invited to complete a questionnaire online together with a caregiver. Data on health care use, quality of life, work status, informal care, and household expenses were collected to estimate costs of DMD from the perspective of society and caregiver households. Results: A total of 770 patients (173 German, 122 Italian, 191 from the United Kingdom, and 284 from the United States) completed the questionnaire. Mean per-patient annual direct cost of illness was estimated at between $23,920 and $54,270 (2012 international dollars), 7 to 16 times higher than the mean per-capita health expenditure in these countries. Indirect and informal care costs were substantial, each constituting between 18% and 43% of total costs. The total societal burden was estimated at between $80,120 and $120,910 per patient and annum, and increased markedly with disease progression. The corresponding household burden was estimated at between $58,440 and $71,900. Conclusions: We show that DMD is associated with a substantial economic burden. Our results underscore the many different costs accompanying a rare condition such as DMD and the considerable economic burden carried by affected families. Our description of the previously unknown economic context of a rare disease serves as important intelligence input to health policy evaluations of intervention programs and novel therapies, financial support schemes for patients and their families, and the design of future cost studies. PMID:24991029

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS) has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs) are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options.

Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punctures were performed in 28 patients 2 to 14 years of age with type 2/3 spinal muscular atrophy. No complications occurred in 50 (68%) lumbar punctures; in 23 (32%) procedures, adverse events were attributed to lumbar puncture. Most common adverse events were headache (n = 9), back pain (n = 9), and post–lumbar puncture syndrome (n = 8). In a subgroup analysis, adverse events were more frequent in older children, children with type 3 spinal muscular atrophy, and with a 21- or 22-gauge needle compared to a 24-gauge needle or smaller. Lumbar punctures were successfully performed in children with spinal muscular atrophy; lumbar puncture–related adverse event frequency was similar to that previously reported in children. PMID:26823478

Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

The lip is an organ consisting mostly of muscle similar to the tongue. While the tongue is known as a muscular hydrostat, it is unclear whether the lip is also. In this paper the muscular hydrostat issue was explored from the anatomical and functional point of view using high-resolution static MRI (hr-MRI 0.125 mm/pixel) and tagged-cineMRI (t-MRI). A 3-D reconstruction of the lips and its muscles was obtained from hr-MRI during sustained vowels /i/ and /u/. The muscular geometry of the orbicularis oris, mentalis, and depressor labii inferior muscles were superimposed onto the principal strains that depicts compression and expansion of the internal tissue obtained from t-MRI. It is shown that (1) orbicularis oris muscle shape can predict both the borderline of glabrous and hairy skin and the manner in which the lips are protruded; (2) the lips volume is almost identical for both speech tasks; and (3) direction and intensity of compression of orbicularis oris and mentalis muscle bundles imply the role of these muscles in the protrusion appearance. These results indicate that the muscular architecture and volume preserving characteristics of the lips are consistent with a muscular hydrostat. [This work was supported by NIH (USA) and NiCT (Japan).

Muscular dystrophy represents a major unmet medical need; only palliative treatments exist for this group of debilitating diseases. Because multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity, a therapeutic approach that can target this loss of membrane function could be applicable to a number of these distinct diseases.One promising therapeutic approach involves the process the cell uses to repair injuries to the plasma membrane. Recent discoveries of genes associated with the membrane repair process provide an opportunity to promote this process as a way to treat muscular dystrophy. One such gene is mitsugumin 53 (MG53), a member of the tripartite motif (TRIM) family of proteins (TRIM72), which is an essential component of the membrane repair pathway in muscle. Recent results indicate that MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types and treat some aspects of the disease in mouse models of muscular dystrophy. There is great potential for the use of recombinant human MG53 in treating muscular dystrophy and other diseases in which compromised membrane integrity contributes to the disease. Other TRIM family proteins may provide additional targets for therapeutic intervention in similar disease states.

The purpose of this manuscript is to address the issue of muscular activity, human motion, fitness, and exercise. Human activity is reviewed from the historical perspective as well as from the basics of muscular contraction, nervous system controls, mechanics, and biomechanical considerations. In addition, attention has been given to some of the principles involved in developing muscular adaptations through strength development. Brief descriptions and findings from a few studies are included. These experiments were conducted in order to investigate muscular adaptation to various exercise regimens. Different theories of strength development were studied and correlated to daily human movements. All measurement tools used represent state of the art exercise equipment and movement analysis. The information presented here is only a small attempt to understand the effects of exercise and conditioning on Earth with the objective of leading to greater knowledge concerning human responses during spaceflight. What makes life from nonliving objects is movement which is generated and controlled by biochemical substances. In mammals. the controlled activators are skeletal muscles and this muscular action is an integral process composed of mechanical, chemical, and neurological processes resulting in voluntary and involuntary motions. The scope of this discussion is limited to voluntary motion.

Muscular dystrophies are a class of disorders that cause progressive muscle wasting. A major hurdle for discovering treatments for the muscular dystrophies is a lack of reliable assays to monitor disease progression in animal models. We have developed a novel mouse model to assess disease activity noninvasively in mice with muscular dystrophies. These mice express an inducible luciferase reporter gene in muscle stem cells. In dystrophic mice, muscle stem cells activate and proliferate in response to muscle degeneration, resulting in an increase in the level of luciferase expression, which can be monitored by noninvasive, bioluminescence imaging. We applied this noninvasive imaging to assess disease activity in a mouse model of the human disease limb girdle muscular dystrophy 2B (LGMD2B), caused by a mutation in the dysferlin gene. We monitored the natural history and disease progression in these dysferlin-deficient mice up to 18 months of age and were able to detect disease activity prior to the appearance of any overt disease manifestation by histopathological analyses. Disease activity was reflected by changes in luciferase activity over time, and disease burden was reflected by cumulative luciferase activity, which paralleled disease progression as determined by histopathological analysis. The ability to monitor disease activity noninvasively in mouse models of muscular dystrophy will be invaluable for the assessment of disease progression and the effectiveness of therapeutic interventions.

Spinal cord injury is associated with adaptations to the muscular, skeletal, and spinal systems. Experimental data are lacking regarding the extent to which rehabilitative methods may influence these adaptations. An understanding of the plasticity of the muscular, skeletal, and spinal systems after paralysis may be important as new rehabilitative technologies emerge in the 21st century. Moreover, individuals injured today may become poor candidates for future scientific advancements (cure) if their neuromusculoskeletal systems are irreversibly impaired. The primary purpose of this paper is to explore the physiological properties of skeletal muscle as a result of spinal cord injury; secondarily, to consider associated changes at the skeletal and spinal levels. Muscular adaptations include a transformation to faster myosin, increased contractile speeds, shift to the right on the torque-frequency curve, increased fatigue, and enhanced doublet potentiation. These muscular adaptations may be prevented in individuals with acute paralysis and partially reversed in individuals with chronic paralysis. Moreover, the muscular changes may be coordinated with motor unit and spinal circuitry adaptations. Concurrently, skeletal adaptations, as measured by bone mineral density, show extensive loss within the first six months after paralysis. The underlying science governing neuromusculoskeletal adaptations after paralysis will help guide professionals as new rehabilitation strategies evolve in the future.

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing. PMID:22000308

Gene therapy for the muscular dystrophies has evolved as a promising treatment for this progressive group of disorders. While corticosteroids and/or supportive treatments remain standard of care for Duchenne muscular dystrophy (DMD), loss of ambulation, respiratory failure and compromised cardiac function is the inevitable outcome. Recent developments in genetically mediated therapies have allowed for personalized treatments that strategically target individual muscular dystrophy subtypes based on disease pathomechanism and phenotype. In this review, we highlight therapeutic progress with emphasis on evolving pre-clinical data and our own experience in completed clinical trials, and others currently underway. We also discuss the lessons we have learned along the way and the strategies developed to overcome limitations and obstacles in this field. PMID:25439576

Duchenne muscular dystrophy is an X-linked, recessively inherited disorder characterized by progressive weakness attributable to the absence of dystrophin expression in muscle. In multiple studies, the chronic administration of corticosteroids slowed the loss of ambulation that develops in mid to late childhood. Corticosteroids, however, frequently produce unacceptable side effects, including Cushingoid appearance and weight gain. Deflazacort, an oxazoline analogue of prednisolone, produces equivalent benefits on muscle with fewer reported Cushingoid side effects. We present a 9-year-old boy with Duchenne muscular dystrophy who developed morbid obesity and subsequent idiopathic intracranial hypertension after 2 years of receiving deflazacort. Although deflazacort is typically thought to produce less obesity than prednisone, severe Cushingoid side effects may occur in some individuals. To our knowledge, this description is the first of idiopathic intracranial hypertension complicating chronic corticosteroid treatment of Duchenne muscular dystrophy.

The outstanding advances in the molecular characterization of muscle diseases, including muscular dystrophies, inflammatory myopathies, and ion channel disorders, have resulted in the identification of potential targets for pharmacologic and genetic therapy in the best characterized of these diseases. The most common myopathy in children, Duchenne muscular dystrophy (DMD), is the focus of active pharmacologic clinical trials. Genetic transfer therapy research for this and other dystrophies is rapidly moving forward. However, as new approaches for treatment are being actively investigated, the current modality of treatment for all myopathies is still in the realm of physical medicine and rehabilitation. The focus of this review is on the advances in pharmacologic and genetic therapy research in DMD and limb girdle muscular dystrophies.

The purpose of the current study was to examine the dimensionality and validity of Yelland and Tiggemann's Drive for Muscularity Scale (YT-DMS). Participants were college students (305 women, M(AGE)=20.15 years, SD=4.00; 356 men, M(AGE)=20.24 years, SD=3.85) who completed the YT-DMS, the Drive for Muscularity Attitudes Questionnaire, the Drive for Leanness Scale, the Drive for Thinness Scale, and a socio-demographic questionnaire. Results indicated the YT-DMS had a stable unidimensional factor structure in both genders, and the pattern of relationships generally supported the measure's criterion and construct validity. These results reveal the YT-DMS has promise, but helps identify possible areas for improvement, such as a greater focus on sampling the content domain associated with the drive for muscularity.

The purpose of this study was to examine the simultaneous relation of general and sport-specific pressures about body weight and shape, negative affect, and body satisfaction to drive for muscularity (DM) in male collegiate athletes. Participants were 183 male athletes who were drawn from three NCAA Division I institutions and represented 17 different sports. As hypothesized, after controlling for BMI and sport type, sport-specific pressures, negative affect, and body satisfaction were significant predictors, and accounted for 15-34% of the variance in muscularity-oriented body image and muscularity behaviors; general pressures however were not significantly related. These findings offer insight into the personal and social antecedents of DM in male athletes, and serve as a starting point for future research on DM in this population.

Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5'untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy.

The aim of this research was to determine the moving and stabilizing functions of selected groups of muscles during the process of static workout. 15 students of the Academy of Physical Education were tested in non-competitive training. Muscular torques achieved during flexing and extending big limb joints were used as the determinant of force. Comparative analysis of torque values achieved in passive stabilization (with support) and muscular stabilization (without support) in elbow and knee joints was carried out. The value of the force applied to the passively stabilizing element in a given measurement during the flexion of elbow and the extension of knee joint was tested. The results of these tests allowed us to learn the value of muscular torques and - after statistical analysis - the relationship between them in particular functions.

Duchenne muscular dystrophy is is the most common form of the childhood muscular dystrophies. It follows a predictable clinical course marked by progressive skeletal muscle weakness, lost of ambulation before teen-age and death in early adulthood secondary to respiratory or cardiac failure. Becker muscular dystrophy is less common and has a milder clinical course but also results in respiratory and cardiac failure.Altough recent advances in respiratory care and new technologies have improved the outlook many patients already received only a traditional non-interventional approach. The aims of this work are: to analyse the pathophysiology and natural history of respiratory function in these diseases, to descript their clinical manifestations, to present the diagnostics tools and to provide recommendations for an adequated respiratory care in this particular population based on the updated literature referenced.

Gene therapy for the muscular dystrophies has evolved as a promising treatment for this progressive group of disorders. Although corticosteroids and/or supportive treatments remain the standard of care for Duchenne muscular dystrophy, loss of ambulation, respiratory failure, and compromised cardiac function is the inevitable outcome. Recent developments in genetically mediated therapies have allowed for personalized treatments that strategically target individual muscular dystrophy subtypes based on disease pathomechanism and phenotype. In this review, we highlight the therapeutic progress with emphasis on evolving preclinical data and our own experience in completed clinical trials and others currently underway. We also discuss the lessons we have learned along the way and the strategies developed to overcome limitations and obstacles in this field.

The muscular dystrophies are a diverse group of genetic disorders without an effective treatment. Because they are caused by mutations in various genes, the most direct way to treat them involves correcting the underlying gene defect (ie, gene therapy). Such a gene therapy approach involves delivering a therapeutic gene cassette to essentially all the muscles of the body in a safe and efficacious manner. The authors describe gene delivery methods using vectors derived from adeno-associated virus that are showing great promise in preclinical studies for treatment of Duchenne muscular dystrophy. It is hoped that variations on these methods might be applicable for most, if not all, of the different types of muscular dystrophy.

Summary Duchenne muscular dystrophy, caused by mutations at the dystrophin gene, is the most common form of Muscular Dystrophy. There is no cure for DMD and current therapeutic approaches to restore dystrophin expression are only partially effective. The absence of dystrophin in muscle results in dysregulation of signaling pathways which could be targets for disease therapy and drug discovery. Previously we identified two exceptional Golden Retriever Muscular Dystrophy (GRMD) dogs that are mildly affected, have functional muscle and normal lifespan despite the complete absence of dystrophin. Now, our data on linkage, whole genome sequencing and transcriptome analyses of these dogs compared to severely affected GRMD and control animals reveal that increased expression of Jagged1 gene, a known regulator of the Notch signaling pathway, is a hallmark of the mild phenotype. Functional analyses demonstrate that Jagged1 overexpression ameliorates the dystrophic phenotype, suggesting that Jagged1 may represent a target for DMD therapy in a dystrophin-independent manner. PMID:26582133

Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA) causes significant disability and progressive functional impairment. Readily available instruments that assess functionality, especially in advanced stages of the disease, are required to monitor the progress of the disease and the impact of therapeutic interventions. To describe the development of a scale to evaluate upper limb function (UL) in patients with DMD and SMA, and describe its validation process, which includes self-training for evaluators. The development of the scale included a review of published scales, an exploratory application of a pilot scale in healthy children and those with DMD, self-training of evaluators in applying the scale using a handbook and video tutorial, and assessment of a group of children with DMD and SMA using the final scale. Reliability was assessed using Cronbach and Kendall concordance and with intra and inter-rater test-retest, and validity with concordance and factorial analysis. A high level of reliability was observed, with high internal consistency (Cronbach a = 0.97), and inter-rater (Kendall W = 0.96) and intra-rater concordance (r = 0.97 to 0.99). The validity was demonstrated by the absence of significant differences between results by different evaluators with an expert evaluator (F = 0.023, p > .5), and by the factor analysis that showed that four factors account for 85.44% of total variance. This scale is a reliable and valid tool for assessing UL functionality in children with DMD and SMA. It is also easily implementable due to the possibility of self-training and the use of simple and inexpensive materials.

This paper is based on the findings of a field study which was planned to ascertain by metabolic measurement the rates of energy expenditure of men and women on productive effort at work in modern factories. The investigation which is described was carried out during a period of peace-time full employment, mainly in factories associated with the Slough Industrial Health Service in which a nutritional survey of the calorie intake of male operatives had been made by the Ministry of Health and the Medical Research Council in 1952. The rates of energy expenditure of 70 men and 54 women in 27 occupational groups were measured by indirect calorimetric methods. On the basis of the criteria for the classification of work according grades to its heaviness, adopted by the Factory Department of the Ministry of Labour, muscular work grades have been ascribed to the occupations studied. From the distribution of 390 metabolic measurements, ranges of energy expenditure have been computed for occupations classed as sedentary, light, moderate, heavy, or very heavy, Observation of recurrent phase variations in types of productive effort in the work-cycle indicated that wider work grades, such as light-to-moderate or moderate-to-heavy, are needed to cover the energy expenditure rates of men and women in many occupations. The data obtained in this study have enabled a table termed the “Slough Scales” to be compiled giving ranges of energy expenditure and pulmonary ventilation rates for the various work grades ascribed to occupations. The mean rates of energy expenditure of 257 workers (in industries in different parts of England and Scotland) which have been calculated from data published by other investigators have been found to fall within the ranges specified in these scales for the work grades of their occupations. It is felt, therefore, that the Slough Scales represent a reasonably true appraisal of the relation between the Ministry of Labour occupational work grades and the

This paper outlines the history of knowledge about the muscular sense and provides a bibliographic resource for further research. A range of different topics, questions and approaches have interrelated throughout this history, and the discussion clarifies this rather than presenting detailed research in any one area. Part I relates the origin of belief in a muscular sense to empiricist accounts of the contribution of the senses to knowledge from Locke, via the iddologues and other authors, to the second half of the nineteenth century. Analysis paid much attention to touch, first in the context of the theory of vision and then in its own right, which led to naming a distinct muscular sense. From 1800 to the present, there was much debate, the main lines of which this paper introduces, about the nature and function of what turned out to be a complex sense. A number of influential psycho-physiologists, notably Alexander Bain and Herbert Spencer, thought this sense the most primitive and primary of all, the origin of knowledge of world, causation and self as an active subject. Part II relates accounts of the muscular sense to the development of nervous physiology and of psychology. In the decades before 1900, the developing separation of philosophy, psychology and physiology as specialised disciplines divided up questions which earlier writers had discussed under the umbrella heading of muscular sensation. The term'kinaesthesia' came in 1880 and 'proprio-ception' in 1906. There was, all the same, a lasting interest in the argument that touch and muscular sensation are intrinsic to the existence of embodied being in the way the other senses are not. In the wider culture--the arts, sport, the psychophysiology of labour and so on--there were many ways in which people expressed appreciation of the importance of what the anatomist Charles Bell had called 'the sixth sense'.

The structure of gastrocnemius tendons from chickens with genetically induced muscular dystrophy has been studied by low-angle X-ray diffraction. Compared with normal samples there is poor alignment of collagen within the tendons. This difference is quite pronounced at eight weeks when the affected birds are still in comparatively good physical condition. Similar changes have been reported for birds with nutritionally induced muscular dystrophy (Bartlett, M. W., Egelstaff, P. A., Holden, T. M., Stinson, R. H. and Sweeny, P. R. (1973) Biochim. Biophys. Acta 328, 213-220).

Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy in humans and syndromes in mice, dogs, and cats. Affected humans and dogs have progressive disease that leads primarily to muscle atrophy. Mdx mice progress through an initial phase of muscle hypertrophy followed by atrophy. Cats have persistent muscle hypertrophy. Hypertrophy in humans has been attributed to deposition of fat and connective tissue (pseudohypertrophy). Increased muscle mass (true hypertrophy) has been documented in animal models. Muscle hypertrophy can exaggerate postural instability and joint contractures. Deleterious consequences of muscle hypertrophy should be considered when developing treatments for muscular dystrophy.

Case report with review describes X-linked muscular dystrophy with contractures in 28 years old man and his cousin. The disease revealed itself in an early stage (age 5-10), the process was progressing with apparent tendons retraction and contraction, limited movement in the areas of the neck and back of spine, atrophy of shoulder and pelvic yard and back muscles. Intellect was intact. Cardyomyopathy was exhibited. CK was normal. EMG showed classic myopathic features. Muscle biopsy showed different caliber groups of muscle fibers, growth of endo-perimesial connective tissue. Clinical manifestations together with electrophysiological and histological data suggest consistency with Rotthauwe-Mortier-Bayer X-linked muscular dystrophy.

Calpain3 is a calcium-dependent intracellular protease involved in an autosomal recessive form of muscular dystrophy known as limb-girdle muscular dystrophy type 2A. Many pathogenic mutations have been identified in calpain3, encoded by the CAPN3 gene, which leads to weakness of the pelvic and shoulder girdle muscles. In the present study, whole exome sequencing was performed on six unrelated Iranian families who presented with progressive muscle weakness, with a strong suspicion of Calpainopathies. Genetic analysis of CAPN3 gene revealed five causative variants which had not been reported in the Iranian population before including a novel 6 bp deletion (c.795_800delCATTGA) and four previously reported mutations (c.1939G > T, c.2243G > A, c.2257delGinsAA, and c.2380 + 2T > G). Our findings indicate that exome sequencing can be a very effective and affordable method to diagnose heterogeneous muscular dystrophies, especially in consanguineous populations such as Iran.

Investigated the drive for muscularity among high school adolescents using the Drive for Muscularity Scale. Results indicated that the scale was reliable. High-drive students were mainly boys trying to gain weight and muscle mass. Drive related to poor self-esteem and higher depression levels among boys, but not girls. Drive for muscularity was…

Muscular dystrophies are genetic muscular disease with disability. Heart failure is a classical complication mainly in Duchenne muscular dystrophy (DMD). We report 2 cases of severe acute heart failure revealed by abdominal discomfort in a patient with DMD and in a patient with gamma-sarcoglycanopathy.

Investigated the drive for muscularity among high school adolescents using the Drive for Muscularity Scale. Results indicated that the scale was reliable. High-drive students were mainly boys trying to gain weight and muscle mass. Drive related to poor self-esteem and higher depression levels among boys, but not girls. Drive for muscularity was…

Facioscapulohumeral muscular dystrophy (FSHD; MIM 158900), is an autosomal dominant neuromuscular disorder. The disease is characterized by the weakness of the muscles of the face, upper-arm and shoulder girdle. The gene for FSHD has been mapped to 4q35 (FSHD1A) and is closely linked to D4F1O4S1, which detects two highly polymorphic loci (located at 4q35 and 10q26), with restriction enzyme EcoRI. The polymorphic EcoRI fragment detected with D4F1O4S1 is composed almost entirely of D4Z4 (3.3 kb) tandem repeats. In FSHD patients a deletion of the integral number of D4Z4 repeats generates a fragment which is usually smaller than 35 kb, whereas in normal controls, the size usually ranges from 50 to 300 kb. These 'small' EcoRI fragments segregate with FSHD in families but appear as de novo deletions in the majority of sporadic cases. Each 3.3 kb repeat contains two homeobox domains neither of which has yet been proven to encode a protein. D4Z4 is located adjacent to the 4q telomere and cross hybridizes to several different regions of the genome. Although D4Z4 probably does not encode a protein with any direct association to FSHD, a clear correlation has been shown between the deletion size at this locus and the age at onset of the disease in FSHD patients. In approximately 5-10% of FSHD families the disease locus is unlinked to 4q35 (locus designated FSHD1B), however, none of the non 4q35 loci for FSHD have yet been chromosomally located. Thus so far, only one gene, FRG1 (FSHD region gene 1) has been identified from the FSHD candidate region on 4q35. The apparent low level of expressed sequences from within this region, the integral deletions of D4Z4 repeats observed in FSHD patients and the close proximity of these repeats to the 4q telomere, all suggest that the disease may be the result of position effect variegation. To date, the molecular diagnosis of FSHD with D4F104S1 has been most secure in those families which are linked to other 4q35 markers. Recent studies

Substantial research has detailed the reading deficits experienced by children with Duchenne muscular dystrophy (DMD). Although phonological awareness (PA) is vital in reading development, little is known about PA in the DMD population. This pilot study describes the PA abilities of a group of five young children with DMD, comparing the results…

Challenges assumptions and research procedures leading to the position that below-average intellectual potential is an integral part of Duchenne muscular dystrophy. A study of 58 boys (ages 5 to 18) from urban, suburban, and rural settings indicated IQ range of 59 to 131 and no evidence of significant verbal deficit (reported in earlier studies).…

Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish, we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor, was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy.

Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

Practical information on children with muscular dystrophy is intended to help parents and teachers facilitate their inclusion in mainstreamed classrooms. Major topics addressed include the following: transportation arrangements; providing full information to the teacher regarding the child's specific abilities and physical limitations;…

The uptake of exogenous /sup 32/Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-(/sup 32/P)ATP, and suggests a possible reinterpretation of those experiments.

Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset. PMID:22701119

Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

The relationships between muscular strength and vertical jumping performance were examined in young women (14-19 years) track and field jumpers (n = 20) and volleyball players (n = 21). The knee extensor muscular strength measured at 9 knee angles was correlated with jumping height and peak power at the squat (SJ) and the countermovement (CMJ) vertical jump tests. Pearson product coefficient of correlation was used to test the significance of these relationships (p = 0.05). The relationships were strong to moderate, but only in the volleyball players (p = 0.05 and power of analysis >0.80). Specifically, in the volleyball players, the strong relationships were noted for muscular strength at the knee angle range of 40 degrees to 90 degrees and CMJ jumping height as well as SJ peak power. Results indicate the dissimilarity in the relationships between the knee extensor muscular strength and jumping performance in the young female track and field jumpers and volleyball players. In addition, it appears that the measure selected to evaluate jumping performance alters the correlational results.

The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO) mice and wild type (WT) mice. The mice were sacrificed at 3, 14, and 28 days post-operation. The results of hematoxylin-eosin staining and immunofluorescence of muscle membrane indicated that muscle regeneration was delayed in p21 KO mice. Cyclin D1 mRNA expression and both Ki-67 and PCNA immunohistochemistry suggested that p21 deficiency increased cell cycle and muscle cell proliferation. F4/80 immunohistochemistry also suggested the increase of immune response in p21 KO mice. On the other hand, both the mRNA expression and western blot analysis of MyoD, myogenin, and Pax7 indicated that muscular differentiation was delayed in p21KO mice. Considering these results, we confirmed that muscle injury causes an increase in cell proliferation. However, muscle differentiation in p21 KO mice was inhibited due to the low expression of muscular synthesis genes, leading to a delay in the muscular regeneration. Thus, we conclude that p21 plays an important role in the in vivo healing process in muscular injury. PMID:25942471

Purpose: We documented speech and voice characteristics associated with oculopharyngeal muscular dystrophy (OPMD). Although it is a rare disease, OPMD offers the opportunity to study the impact of myopathic weakness on speech production in the absence of neurologic deficits in a relatively homogeneous group of speakers. Methods: Twelve individuals…

Purpose: We documented speech and voice characteristics associated with oculopharyngeal muscular dystrophy (OPMD). Although it is a rare disease, OPMD offers the opportunity to study the impact of myopathic weakness on speech production in the absence of neurologic deficits in a relatively homogeneous group of speakers. Methods: Twelve individuals…

Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

Practical information on children with muscular dystrophy is intended to help parents and teachers facilitate their inclusion in mainstreamed classrooms. Major topics addressed include the following: transportation arrangements; providing full information to the teacher regarding the child's specific abilities and physical limitations;…

Substantial research has detailed the reading deficits experienced by children with Duchenne muscular dystrophy (DMD). Although phonological awareness (PA) is vital in reading development, little is known about PA in the DMD population. This pilot study describes the PA abilities of a group of five young children with DMD, comparing the results…

Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

Challenges assumptions and research procedures leading to the position that below-average intellectual potential is an integral part of Duchenne muscular dystrophy. A study of 58 boys (ages 5 to 18) from urban, suburban, and rural settings indicated IQ range of 59 to 131 and no evidence of significant verbal deficit (reported in earlier studies).…

During the earliest stages of resistance exercise training, initial muscular strength gains occur too rapidly to be explained solely by muscle-based mechanisms. However, increases in surface-based EMG amplitude as well as motor unit discharge rate provide some insight to the existence of neural mechanisms in the earliest phases of resistance…

A 13-hour-old Aberdeen-Angus was involuntarily recumbent since birth. Congenital nutritional muscular dystrophy was suspected based on clinical findings, increased serum creatine kinase, and decreased serum vitamin E and selenium levels. Recovery followed after supportive therapy and parenteral vitamin E and selenium. Reports of this disease in newborn calves are unusual.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the absence of dystrophin, a sarcolemmal protein which links the cytoskeleton to the extracellular matrix by interacting with a large number of proteins. Heart failure is a classic complication of this disease. The authors review the pathogenesis and therapeutics of cardiac involvement in DMD.

Mutations in laminin α2-subunit (Lmα2, encoded by LAMA2) are linked to approximately 30% of congenital muscular dystrophy cases. Mice with a homozygous mutation in Lama2 (dy2J mice) express a nonpolymerizing form of laminin-211 (Lm211) and are a model for ambulatory-type Lmα2-deficient muscular dystrophy. Here, we developed transgenic dy2J mice with muscle-specific expression of αLNNd, a laminin/nidogen chimeric protein that provides a missing polymerization domain. Muscle-specific expression of αLNNd in dy2J mice resulted in strong amelioration of the dystrophic phenotype, manifested by the prevention of fibrosis and restoration of forelimb grip strength. αLNNd also restored myofiber shape, size, and numbers to control levels in dy2J mice. Laminin immunostaining and quantitation of tissue extractions revealed increased Lm211 expression in αLNNd-transgenic dy2J mice. In cultured myotubes, we determined that αLNNd expression increased myotube surface accumulation of polymerization-deficient recombinant laminins, with retention of collagen IV, reiterating the basement membrane (BM) changes observed in vivo. Laminin LN domain mutations linked to several of the Lmα2-deficient muscular dystrophies are predicted to compromise polymerization. The data herein support the hypothesis that engineered expression of αLNNd can overcome polymerization deficits to increase laminin, stabilize BM structure, and substantially ameliorate muscular dystrophy.

Study of the effects of brief exercise on mental processes by Tomporowski and Ellis (1986) has shown that moderate muscular tension improves cognitive performance while low or high tension does not. Improvements in performance induced by exercise are commonly associated with increase in arousal, while impairments are generally attributed to the effects of muscular or central fatigue. To test two hypotheses, that (1) submaximal muscular exercise would decrease premotor time and increase would increase the attentional and preparatory effects observed in premotor time 9 men, aged 20 to 30 years, performed an isometric test at 50% of their maximum voluntary contraction between blocks of a 3-choice reaction-time fencing task. Analysis showed (1) physical exercise did not improve postexercise premotor time, (2) muscular fatigue induced by isometric contractions did not increase motor time, (3) there was no effect of exercise on attentional and preparatory processes involved in the postexercise choice-RT task. The invalidation of hypotheses was mainly explained by disparity in directional effects across subjects and by use of an exercise that was not really fatiguing.

Ehlers-Danlos syndrome includes 11 distinct entities. The diversity of this collagen dysplasia and its combination with other abnormalities make it difficult to understand physiopathologically. A case of Ehlers-Danlos syndrome is reported, which is novel owing to its combination with clotting abnormalities and especially with muscular dystrophy. To our knowledge this has not previously been reported. The patient was a young man aged 16 years who presented with Ehlers-Danlos syndrome satisfying Perelman's diagnostic criteria. His father and two brothers had comparable clinical symptoms, but his mother and sister were healthy. The four male subjects had an increased cephalin-kaolin time, reduced levels of factor VIII and Willebrand's factor (but without haemophilia A or Willebrand's disease), and, especially, an abnormal platelet ATP secretion. The proband alone had muscular disease with bilateral quadriceps fatigability and amyotrophy. The muscle enzyme levels were greatly increased, the electromyographic trace was myogenic, and the biopsy showed severe muscular dystrophy. This new observation poses the problem of the relation between clotting abnormalities and collagen abnormalities in the Ehlers-Danlos syndrome. It is difficult to classify this case within any of the 11 known types because of its muscular manifestations. It may perhaps be a fortuitous combination or an extension of the nosological framework of this syndrome. Images PMID:2512864

Phenotypic expression in the muscular dystrophies is variable, even with the identical mutation, providing strong evidence that genetic modifiers influence outcome. To identify genetic modifier loci, we used quantitative trait locus mapping in two differentially affected mouse strains with muscular dystrophy. Using the Sgcg model of limb girdle muscular dystrophy that lacks the dystrophin-associated protein γ-sarcoglycan, we evaluated chromosomal regions that segregated with two distinct quantifiable characteristics of muscular dystrophy, membrane permeability and fibrosis. We previously identified a single major locus on murine chromosome 7 that influences both traits of membrane permeability and fibrosis in the quadriceps muscle. Using a larger cohort, we now found that this same interval strongly associated with both traits in all limb skeletal muscle groups studied, including the gastrocnemius/soleus, gluteus/hamstring, and triceps muscles. In contrast, the muscles of the trunk were modified by distinct genetic loci, possibly reflecting the embryological origins and physiological stressors unique to these muscle groups. A locus on chromosome 18 was identified that modified membrane permeability of the abdominal muscles, and a locus on chromosome 3 was found that regulated diaphragm and abdominal muscle fibrosis. Fibrosis in the heart associated with a region on chromosome 9 and likely reflects differential function between cardiac and skeletal muscle. These data underscore the complexity of inheritance and penetrance of single-gene disorders. PMID:20959497

Duchenne muscular dystrophy is a debilitating X-linked disease with limited treatment options. We examined the possibility of moving forward with gene therapy, an approach that demonstrates promise for treating Duchenne muscular dystrophy. Gene therapy is not limited to replacement of defective genes but also includes strategies using surrogate genes with alternative but effective means of improving cellular function or repairing gene mutations. The first viral-mediated gene transfer for any muscle disease was carried out at Columbus Children's Research Institute and Ohio State University for limb girdle muscular dystrophy type 2D, and the first viral-mediated trial of gene transfer for Duchenne muscular dystrophy is under way at the same institutions. These studies, consisting of intramuscular injection of virus into a single muscle, are limited in scope and represent phase 1 clinical trials with safety as the primary end point. These initial clinical studies lay the foundation for future studies, providing important information about dosing, immunogenicity, and viral serotype in humans. This article highlights the challenges and potential pitfalls as the field advances this treatment modality to clinical reality.

Muscular dystrophy arises from ongoing muscle degeneration and insufficient regeneration. This imbalance leads to loss of muscle, with replacement by scar or fibrotic tissue, resulting in muscle weakness and, eventually, loss of muscle function. Human muscular dystrophy is characterized by a wide range of disease severity, even when the same genetic mutation is present. This variability implies that other factors, both genetic and environmental, modify the disease outcome. There has been an ongoing effort to define the genetic and molecular bases that influence muscular dystrophy onset and progression. Modifier genes for muscle disease have been identified through both candidate gene approaches and genome-wide surveys. Multiple lines of experimental evidence have now converged on the transforming growth factor-β (TGF-β) pathway as a modifier for muscular dystrophy. TGF-β signaling is upregulated in dystrophic muscle as a result of a destabilized plasma membrane and/or an altered extracellular matrix. Given the important biological role of the TGF-β pathway, and its role beyond muscle homeostasis, we review modifier genes that alter the TGF-β pathway and approaches to modulate TGF-β activity to ameliorate muscle disease.

Duchenne muscular dystrophy is an inherited fatal genetic disease characterized by mutations in dystrophin gene, causing membrane fragility leading to myofiber necrosis and inflammatory cell recruitment in dystrophic muscles. The resulting environment enriched in proinflammatory cytokines, like IFN-γ and TNF-α, determines the transformation of myofiber constitutive proteasome into the immunoproteasome, a multisubunit complex involved in the activation of cell-mediate immunity. This event has a fundamental role in producing peptides for antigen presentation by MHC class I, for the immune response and also for cytokine production and T-cell differentiation. Here, we characterized for the first time the presence of T-lymphocytes activated against revertant dystrophin epitopes, in the animal model of Duchenne muscular dystrophy, the mdx mice. Moreover, we specifically blocked i-proteasome subunit LMP7, which was up-regulated in dystrophic skeletal muscles, and we demonstrated the rescue of the dystrophin expression and the amelioration of the dystrophic phenotype. The i-proteasome blocking lowered myofiber MHC class I expression and self-antigen presentation to T cells, thus reducing the specific antidystrophin T cell response, the muscular cell infiltrate, and proinflammatory cytokine production, together with muscle force recovery. We suggest that i-proteasome inhibition should be considered as new promising therapeutic approach for Duchenne muscular dystrophy pathology.

Muscular dystrophies are heterogeneous neuromuscular disorders of inherited origin, including Duchenne muscular dystrophy (DMD). Cell-based therapies were used to promote muscle regeneration with the hope that the host cells repopulated the muscle and improved muscle function and pathology. Stem cells were preferable for therapeutic applications, due to their capacity of self-renewal and differentiative potential. In the last years, encouraging results were obtained with adult stem cells to treat muscular dystrophies. Adult stem cells were found into various tissues of the body and they were able to maintain, generate, and replace terminally differentiated cells within their own specific tissue because of cell turnover or tissue injury. Moreover, it became clear that these cells could participate into regeneration of more than just their resident organ. Here, we described multiple types of muscle and non muscle-derived myogenic stem cells, their characterization and their possible use to treat muscular dystrophies. We also underlined that most promising possibility for the management and therapy of DMD is a combination of different approaches, such as gene and stem cell therapy.

During the earliest stages of resistance exercise training, initial muscular strength gains occur too rapidly to be explained solely by muscle-based mechanisms. However, increases in surface-based EMG amplitude as well as motor unit discharge rate provide some insight to the existence of neural mechanisms in the earliest phases of resistance…

New Findings What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X‐linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene‐replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re‐establish muscle function. PMID:26140505

Set shifting difficulties and weak central coherence are information-processing biases associated with thinness-oriented eating and body image pathology in women. However, little is known about the relationship between these processing biases and muscularity-oriented eating and body image pathology. We investigated whether set shifting and central coherence were uniquely related to the drive for muscularity and muscularity-oriented disordered eating in a sample of 91 male undergraduates. Participants completed the Wisconsin Card Sort Test, the Matching Familiar Figures Task, the Drive for Muscularity scale, and a modified Eating Disorders Examination-Questionnaire. Results indicated that set shifting difficulties and weak central coherence were both uniquely positively associated with the drive for muscularity, and that set shifting difficulties were uniquely positively associated with muscularity-oriented disordered eating. Results are discussed with regard to the male experience of body image and eating pathology, and in regard to muscle dysmorphia.

Increased fear of falling is associated with greater muscular coactivation during standing postural control. Excessive muscular coactivation reduces the performance of agonist muscles. Although several recent studies have observed increased muscular coactivation during walking in older adults, little is known about the relationship between fear of falling and muscular coactivation during walking. The purpose of this study was to compare muscular coactivation during walking between older adults with fear of falling and older adults without fear of falling. Thirty-eight healthy older adults (82.3 ± 6.8 years) participated in this study. Walking speed and step length were measured. Electromyography (EMG) data were collected from the tibialis anterior and soleus during walking to calculate the co-contraction index (CI). Subjects were divided into those with fear of falling and those without fear of falling, on the basis of a modified Falls Efficacy Scale (FES). Stepwise multiple regression analysis was used, with CI as the dependent variable, and fear of falling, experience of falling (during the past year), walking speed, step length, and age as independent variables. Mean values of CI during walking, walking speed, and step length were 51.9 ± 11.7%, 0.90 ± 0.40 m/s, and 0.43±0.11 m, respectively. Eight subjects (21.1%) had fallen within the past year, and 19 subjects (50.0%) had fear of falling. All subjects without fear of falling had FES scores of 10 (maximum score). Subjects with fear of falling had a median FES score of 17 (interquartile range, 13 to 25). Stepwise multiple regression analysis revealed that fear of falling remained significantly associated with CI (p<0.01): CIs for subjects with fear and those without fear were 59.5 ± 12.2% and 46.7 ± 8.5%, respectively. Individuals with a fear of falling have increased muscular co-activation at the ankle joint during walking, at least in a certain subgroup of older adults. Further research is needed to

More than 100 genetic mutations causing X-linked Emery-Dreifuss muscular dystrophy have been identified in the gene encoding the integral inner nuclear membrane protein emerin. Most mutations are nonsense or frameshift mutations that lead to the absence of emerin in cells. Only very few cases are due to missense or short in-frame deletions. Molecular mechanisms explaining the corresponding emerin variants' loss of function are particularly difficult to identify because of the mostly intrinsically disordered state of the emerin nucleoplasmic region. We now demonstrate that this EmN region can be produced as a disordered monomer, as revealed by nuclear magnetic resonance, but rapidly self-assembles in vitro. Increases in concentration and temperature favor the formation of long curvilinear filaments with diameters of approximately 10 nm, as observed by electron microscopy. Assembly of these filaments can be followed by fluorescence through Thioflavin-T binding and by Fourier-transform Infrared spectrometry through formation of β-structures. Analysis of the assembly properties of five EmN variants reveals that del95-99 and Q133H impact filament assembly capacities. In cells, these variants are located at the nuclear envelope, but the corresponding quantities of emerin-emerin and emerin-lamin proximities are decreased compared to wild-type protein. Furthermore, variant P183H favors EmN aggregation in vitro, and variant P183T provokes emerin accumulation in cytoplasmic foci in cells. Substitution of residue Pro183 might systematically favor oligomerization, leading to emerin aggregation and mislocalization in cells. Our results suggest that emerin self-assembly is necessary for its proper function and that a loss of either the protein itself or its ability to self-assemble causes muscular dystrophy.

We examined the characteristics of dysphagia in spinal and bulbar muscular atrophy, a hereditary neuromuscular disease causing weakness of limb, facial, and oropharyngeal muscles via a videofluoroscopic swallowing study, and investigated the plausibility of using these outcome measures for quantitative analysis. A videofluoroscopic swallowing study was performed on 111 consecutive patients with genetically confirmed spinal and bulbar muscular atrophy and 53 age- and sex-matched healthy controls. Swallowing of 3-mL liquid barium was analyzed by the Logemann's Videofluorographic Examination of Swallowing worksheet. Of more than 40 radiographic findings, the most pertinent abnormal findings in patients with spinal and bulbar muscular atrophy, included vallecular residue after swallow (residue just behind the tongue base), nasal penetration, and insufficient tongue movement (P muscular atrophy, laryngeal penetration was observed more frequently in those without subjective dysphagia. Dysphagia of spinal and bulbar muscular atrophy was characterized by impaired tongue movement in the oral phase and nasal penetration followed by pharyngeal residues, which resulted in multiple swallowing sessions and laryngeal penetration. Although major limitations of reproducibility and radiation exposure still exist with videofluoroscopy, pharyngeal residue after initial swallowing and the penetration-aspiration scale might serve as potential outcome measures in clinical studies.

We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.

This project examined whether interpersonal pressure to be muscular predicted late adolescents’ pursuit of muscularity. Participants were 199 adolescents (16–19 years), mothers (n=175), and friends (n=159), assessed at two annual times. Pressure to be muscular was assessed with adolescents’, mothers’, and friends’ reports of their relationships. Adolescents reported pressure from fathers and romantic partners, appearance satisfaction, disordered eating, and pursuit of muscularity. Adolescents,’ mothers’, and friends’ reports of pressure related to pursuit of muscularity at both times. Adolescents’ perceptions and mothers’ reports prospectively predicted pursuit of muscularity. Findings highlight the relevance of relationships to pursuit of muscularity in late adolescents. PMID:20348360

Autosomal dominant congenital spinal muscular atrophy is characterized by predominantly lower limb weakness and wasting, and congenital or early-onset contractures of the hip, knee and ankle. Mutations in TRPV4, encoding a cation channel, have recently been identified in one large dominant congenital spinal muscular atrophy kindred, but the genetic basis of dominant congenital spinal muscular atrophy in many families remains unknown. It has been hypothesized that differences in the timing and site of anterior horn cell loss in the central nervous system account for the variations in clinical phenotype between different forms of spinal muscular atrophy, but there has been a lack of neuropathological data to support this concept in dominant congenital spinal muscular atrophy. We report clinical, electrophysiology, muscle magnetic resonance imaging and histopathology findings in a four generation family with typical dominant congenital spinal muscular atrophy features, without mutations in TRPV4, and in whom linkage to other known dominant neuropathy and spinal muscular atrophy genes has been excluded. The autopsy findings in the proband, who died at 14 months of age from an unrelated illness, provided a rare opportunity to study the neuropathological basis of dominant congenital spinal muscular atrophy. There was a reduction in anterior horn cell number in the lumbar and, to a lesser degree, the cervical spinal cord, and atrophy of the ventral nerve roots at these levels, in the absence of additional peripheral nerve pathology or abnormalities elsewhere along the neuraxis. Despite the young age of the child at the time of autopsy, there was no pathological evidence of ongoing loss or degeneration of anterior horn cells suggesting that anterior horn cell loss in dominant congenital spinal muscular atrophy occurs in early life, and is largely complete by the end of infancy. These findings confirm that dominant congenital spinal muscular atrophy is a true form of spinal

Data sourcesMedline via Pubmed and the Cochrane Library were searched from January 1980 to September 2013. This was complemented by a manual search of the magazines Deutsche Zahnaerztliche Zeitung, Quintessenz, Zeitschrift für Zahnärztliche Implantologie, Schweizerische Monatszeitschrift and Implantologie. Additionally, the list of reference s of all selected full-text articles and related reviews were further scrutinised for potential included studies in English or German.Study selectionThree review authors independently searched for clinical trials that assessed the muscular activity in the intervention groups: edentulous patients treated with implant-overdentures (IODs) and implant-supported fixed dental prostheses (ISFDPs) and the comparison groups: dentates and edentulous patients treated with mucosa-borne complete removable dental prostheses (CRDPs).Data extraction and synthesisThe primary outcome was the muscular activity (measured by electromyography [EMG]) in masseter or temporalis muscle of the participants during clenching and chewing. The data extraction of each included study consisted of author, year, age range, treatment, number of participants, number of implants inserted, arch treated, opposite jaw, kind and side of the muscles that were measured. EMG gain or loss (unit measured: volt) was considered by using the effect size. For the meta-analyses only the studies that included masseter muscle measured separately from temporalis were considered. Concerning the side of measurement (right and left side measured together or right and left side measured separately), only the dominant type in each category was included.ResultsSixteen articles, out of the initial 646 retrieved abstracts, were analysed. The muscular activity of edentulous subjects increased after implant support therapy during clenching (effect size [ES]: 2.18 [95% confidence interval [CI]: 1.14, 3.23]) and during chewing (ES: 1.45 [95 % CI: 1.21, 1.69]). In addition, the pooled EMG

Muscular dystrophies result from a defect in the linkage between the muscle fiber cytoskeleton and the basement membrane (BM). Congenital muscular dystrophy type MDC1A is caused by mutations in laminin α2 that either reduce its expression or impair its ability to polymerize within the muscle fiber BM. Defects in this BM lead to muscle fiber damage from the force of contraction. In this issue of the JCI, McKee and colleagues use a laminin polymerization-competent, designer chimeric BM protein in vivo to restore function of a polymerization-defective laminin, leading to normalized muscle structure and strength in a mouse model of MDC1A. Delivery of such a protein to patients could ameliorate many aspects of their disease.

We recorded scalp electrical activity before and after full neuro-muscular paralysis in 5 volunteers and determined differences due to elimination of muscular activity on several standard applications of EEG. Due to paralysis, there were reductions in 'noisiness' of the standard scalp recordings which were maximal over the peripheral scalp, not explained by abolition of movement artefact, and best accounted for by sustained EMG activity in resting individuals. There was a corresponding reduction in spectral power in the gamma range. In central leads, the extent of gamma frequency coherence during a non-time-locked mental task (1 s epochs) was reduced by paralysis, likely due to a reduction in gamma-frequency coherence in widely arising EMG signals. In a time-locked mental task (auditory oddball), evoked responses were qualitatively unaffected by paralysis but 3 of 4 induced gamma responses were obscured by EMG.

Studies have shown that dispositional mindfulness, a construct characterized by awareness and attention to present moment experiences, is associated with body image constructs in women. However, little is known about the relationship between dispositional mindfulness and body image among men. Therefore, this study examined the unique associations between dispositional mindfulness and three body image variables in men: overall appearance evaluation, satisfaction with distinct body areas, and drive for muscularity. Undergraduate men (N=296) completed the Multidimensional Body Self-Relations Questionnaire-Appearance Scales, the Drive for Muscularity Scale, the Mindful Attention Awareness Scale, and the Positive and Negative Affect Schedule. A series of hierarchical regression analyses revealed that mindfulness was uniquely associated with all three body image variables after accounting for body mass index and negative affect. Results are discussed with regard to the potential role of dispositional mindfulness in body dissatisfaction among men.

Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.

SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem cell divisions and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility, but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review, we highlight recent research advances in DMD and discuss the current state of treatment and importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD. PMID:27161598

Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

This study analyzes the performance of knee extension and flexion of Taekwondo and Kickboxing athletes. The power values were extracted through electromyography obtained by an isokinetic dynamometer at 60 degrees per second. These values are resulted from the square of the electromyography signal. The analysis of kick power was made using a modified wavelet algorithm considering values with 95% significance. Both groups presented equivalent power and torque capacity with different training times and experience, on the other hand, the wavelet analysis showed better results in muscular recruitment performance in athletes with more experience, in other words, power is not only performance but also power plus recruitment produces better results. This study uniquely showed that muscular enhancement capacity is not only related to the power capacity of contraction but also to motor coordination.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are caused by mutations in the dystrophin-encoding DMD gene. Large deletions and duplications are most common, but small mutations have been found as well. Having a correct diagnosis is important for family planning and providing proper care to patients according to published guidelines. With mutation-specific therapies under development for DMD, a correct diagnosis is now also important for assessing whether patients are eligible for treatments. This review discusses different mutations causing DMD, diagnostic techniques available for making a genetic diagnosis for children suspected of DMD and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies for DMD. PMID:26754139

Muscular dystrophies are groups of inherited progressive diseases of the muscle caused by mutations of diverse genes related to normal muscle function. Although there is no current effective treatment for these devastating diseases, various molecular strategies have been developed to restore the expressions of the associated defective proteins. In preclinical animal models, both viral and nonviral vectors have been shown to deliver recombinant versions of defective genes. Antisense oligonucleotides have been shown to modify the splicing mechanism of mesenger ribonucleic acid to produce an internally deleted but partially functional dystrophin in an experimental model of Duchenne muscular dystrophy. In addition, chemicals can induce readthrough of the premature stop codon in nonsense mutations of the dystrophin gene. On the basis of these preclinical data, several experimental clinical trials are underway that aim to demonstrate efficacy in treating these devastating diseases. PMID:20944811

In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.

The human attention system is based on the capability of the eye of focusing and tracking. These actions are performed by the eyeball muscle system, as a consequence of visual stimuli. The F.A.C.E. (Facial Automaton for Conveying Emotions) project at our lab concerns the development of an android face endowed with dynamic expressiveness and artificial vision. Aimed at realising an artificial attention system for such an automaton, we present here a study for the development of pseudo-muscular polymer actuators for its eyeballs. The system is based on the mimicry of the muscular architecture of the human eye. In particular, linear actuators made of dielectric elastomers have been designed to replicate actions exerted by the main ocular muscles.

The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. This study evaluated the strength-HTN association with and without accounting for CRF. Participants were 4147 men (age = 20-82 yr) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a one-repetition maximal leg and a one-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals of incident HTN events according to exposure categories. During a mean follow-up of 19 yr, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HR of HTN in normotensive men comparing middle- and high-strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HR of HTN in baseline prehypertensive men comparing middle- and high-strength thirds to the lowest third were significant at 0.73 and 0.72 (P = 0.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (P = 0.26). The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF.

The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. Purpose This study evaluated the strength-HTN association with and without accounting for CRF. Methods Participants were 4147 men (20–82 years) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a 1-repetition maximal leg and a 1-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals of incident HTN events according to exposure categories. Results During a mean follow-up of 19 years, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HRs of hypertension in normotensive men comparing middle and high strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HRs of hypertension in baseline prehypertensive men comparing middle and high strength thirds to the lowest third were significant at 0.73 and 0.72 (p=.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (p=.26). Conclusions The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF. PMID:19927030

Our Translational Gene Therapy Center has used small molecules for exon skipping and mutation suppression and gene transfer to replace or provide surrogate genes as tools for molecular-based approaches for the treatment of muscular dystrophies. Exon skipping is targeted at the pre-mRNA level allowing one or more exons to be omitted to restore the reading frame. In Duchenne Muscular Dystrophy (DMD), clinical trials have been performed with two different oligomers, a 2′O-methyl-ribo-oligonucleoside-phosphorothioate (2′OMe) and a phosphorodiamidate morpholino (PMO). Both have demonstrated early evidence of efficacy. A second molecular approach involves suppression of stop codons to promote readthrough of the DMD gene. We have been able to establish proof of principle for mutation suppression using the aminoglycoside, gentamicin. A safer, orally administered, alternative agent referred to as Ataluren (PTC124) has been used in clinical trials and is currently under consideration for approval by the FDA. Using a gene therapy approach, we have completed two trials and have initiated a third. For DMD, we used a mini-dystrophin transferred in adeno-associated virus (AAV). In this trial an immune response was seen directed against transgene product, a quite unexpected outcome that will help guide further studies. For limb girdle muscular dystrophy 2D (alpha-sarcoglycan deficiency), the transgene was again transferred using AAV but in this study, a muscle specific creatine kinase promoter controlled gene expression that persisted for six months. A third gene therapy trial has been initiated with transfer of the follistatin gene in AAV directly to the quadriceps muscle. Two diseases with selective quadriceps muscle weakness are undergoing gene transfer including sporadic inclusion body myositis (sIBM) and Becker muscular dystrophy (BMD). Increasing the size and strength of the muscle is the goal of this study. Most importantly, no adverse events have been encountered in

Duchenne muscular dystrophy (DMD) is a devastating progressive disease for which there is currently no effective treatment except palliative therapy. There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene. The lessons learned from these approaches will be applicable to many other disorders.

Our Translational Gene Therapy Center has used small molecules for exon skipping and mutation suppression and gene transfer to replace or provide surrogate genes as tools for molecular-based approaches for the treatment of muscular dystrophies. Exon skipping is targeted at the pre-mRNA level allowing one or more exons to be omitted to restore the reading frame. In Duchenne Muscular Dystrophy (DMD), clinical trials have been performed with two different oligomers, a 2'O-methyl-ribo-oligonucleoside-phosphorothioate (2'OMe) and a phosphorodiamidate morpholino (PMO). Both have demonstrated early evidence of efficacy. A second molecular approach involves suppression of stop codons to promote readthrough of the DMD gene. We have been able to establish proof of principle for mutation suppression using the aminoglycoside, gentamicin. A safer, orally administered, alternative agent referred to as Ataluren (PTC124) has been used in clinical trials and is currently under consideration for approval by the FDA. Using a gene therapy approach, we have completed two trials and have initiated a third. For DMD, we used a mini-dystrophin transferred in adeno-associated virus (AAV). In this trial an immune response was seen directed against transgene product, a quite unexpected outcome that will help guide further studies. For limb girdle muscular dystrophy 2D (alpha-sarcoglycan deficiency), the transgene was again transferred using AAV but in this study, a muscle specific creatine kinase promoter controlled gene expression that persisted for six months. A third gene therapy trial has been initiated with transfer of the follistatin gene in AAV directly to the quadriceps muscle. Two diseases with selective quadriceps muscle weakness are undergoing gene transfer including sporadic inclusion body myositis (sIBM) and Becker muscular dystrophy (BMD). Increasing the size and strength of the muscle is the goal of this study. Most importantly, no adverse events have been encountered in any of

Halofuginone is a leading agent in preventing fibrosis and inflammation in various muscular dystrophies. We hypothesized that in addition to these actions, halofuginone directly promotes the cell-cycle events of satellite cells in the mdx and dysf(-/-) mouse models of early-onset Duchenne muscular dystrophy and late-onset dysferlinopathy, respectively. In both models, addition of halofuginone to freshly prepared single gastrocnemius myofibers derived from 6-week-old mice increased BrdU incorporation at as early as 18h of incubation, as well as phospho-histone H3 (PHH3) and MyoD protein expression in the attached satellite cells, while having no apparent effect on myofibers derived from wild-type mice. BrdU incorporation was abolished by an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated protein kinase, suggesting involvement of this pathway in mediating halofuginone's effects on cell-cycle events. In cultures of myofibers and myoblasts isolated from dysf(-/-) mice, halofuginone reduced Bax and induced Bcl2 expression levels and induced Akt phosphorylation in a time-dependent manner. Addition of an inhibitor of the phosphinositide-3-kinase/Akt pathway reversed the halofuginone-induced cell survival, suggesting this pathway's involvement in mediating halofuginone's effects on survival. Thus, in addition to its known role in inhibiting fibrosis and inflammation, halofuginone plays a direct role in satellite cell activity and survival in muscular dystrophies, regardless of the mutation. These actions are of the utmost importance for improving muscle pathology and function in muscular dystrophies.

With muscular training, the central nervous system may regulate motor unit firing rates to sustain force output and delay fatigue. The aims of this study were to investigate motor unit firing rates and patterns of the adductor pollicis (AdP) muscle in young, able-bodied adults throughout a sustained submaximal isometric fatiguing contraction and postactivation potentiation pre-post 4 weeks of muscular endurance training. Fifteen participants (training group: N = 10; control group: N = 5) performed maximal voluntary contractions (MVCs) and a sustained isometric 20 % MVC fatigue task pre-post training. Single-motor-unit potentials were recorded from the AdP during the fatigue task with intramuscular fine-wire electrodes. Twitch force potentiation was measured during single-pulse electrical stimulation of the ulnar nerve before and after MVCs. The training group endurance trained their AdP muscle at 20 % MVC for 4 weeks. Mean motor unit firing rates were calculated every 5 % of endurance time (ET). ET increased by 45.2 ± 8.7 % (p < 0.001) following muscular endurance training. Although ET increased, mean motor unit firing rates during the fatigue task did not change significantly with training. The general motor unit firing pattern consisted of an initial slowing followed by an increase in firing rate late in fatigue and remained consistent pre-post training. Potentiation did not change following training. These data suggest that the ability of the neuromuscular system to sustain motor unit firing rate may serve as a mechanism to augment the duration of submaximal muscle performance and delay muscular fatigue.

In skeletal muscle, dystroglycan (DG) is the central component of the dystrophin-glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1) have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others) model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle-wasting disease caused by mutations in the dystrophin gene. Although dystrophin deficiency in myofiber triggers the disease’s pathological changes, the degree of satellite cell (SC) dysfunction defines disease progression. Here, we have identified chicken ovalbumin upstream promoter–transcription factor II (COUP-TFII) hyperactivity as a contributing factor underlying muscular dystrophy in a dystrophin-deficient murine model of DMD. Ectopic expression of COUP-TFII in murine SCs led to Duchenne-like dystrophy in the muscles of control animals and exacerbated degenerative myopathies in dystrophin-deficient mice. COUP-TFII–overexpressing mice exhibited regenerative failure that was attributed to deficient SC proliferation and myoblast fusion. Mechanistically, we determined that COUP-TFII coordinated a regenerative program through combined regulation of multiple promyogenic factors. Furthermore, inhibition of COUP-TFII preserved SC function and counteracted the muscle weakness associated with Duchenne-like dystrophy in the murine model, suggesting that targeting COUP-TFII is a potential treatment for DMD. Together, our findings reveal a regulatory role of COUP-TFII in the development of muscular dystrophy and open up a potential therapeutic opportunity for managing disease progression in patients with DMD. PMID:27617862

In archery shooting, the archer should hold the bow in place using only the pressure produced through drawing back the bowstring. Most coaches discourage the archer from gripping the bow as this is believed to produce a sideways deflecting torque on the bow and arrow during the release. The purpose of this study was to compare the bow hand forearm muscular activation patterns of elite archers with beginners to define the muscular contraction-relaxation strategies in the bow hand forearm muscles during archery shooting and investigate the effects of performance level on these strategies. Electromyographic activity of the M. flexor digitorum superficialis and the M. extensor digitorum of 10 elite and 10 beginner archers were recorded together with a pulse synchronized with the clicker snap. Raw electromyographic records as 1s before and after the clicker pulse were rectified, integrated, and normalized. The data was then averaged for successive shots of each subject and later for both groups of archers. The main difference between the elite and beginner archers was that the elite archers had a greater activation of the M. extensor digitorum, which indicates that they avoid gripping the bow-handle not only relaxing the flexor muscles, but also contracting the extensor muscle groups. This muscular contraction strategy secures the archer to not interfere with the forward movement of the bow, which is the forward acceleration of the bow caused by the pushing power of the bowstring.

OBJECTIVE: In overhead sports such as volleyball, baseball, or tennis shoulder problems are very common. The aim of this study was to identify features which may correlate with shoulder problems in volleyball attackers. METHODS: 30 competitive volleyball attackers (mean age 25 years) were included in the study; 15 were suffering from shoulder pain and 15 had no history of shoulder pain. The results were compared with those of a control group of 15 recreational athletes without any overhead sports activities. RESULTS: Volleyball attackers have a different muscular and capsular pattern at the playing shoulder compared to the opposite shoulder. Their playing shoulder is depressed, the scapula lateralised, and the dorsal muscles and the posterior and inferior part of the shoulder capsule shortened. These differences were of more significance in volleyball attackers with shoulder pain than in volleyball players without shoulder pain. In contrast to recreational athletes without any overhead sports activity, there were no significant difference in the comparison of the two shoulders. The histories, clinical and sonographic findings did not reveal further typical features for volleyball attackers with shoulder pain. CONCLUSIONS: Muscular balance of the shoulder girdle is very important in this sport. It is therefore imperative to include adequate stretching and muscular training programme for the prevention, as well as for therapy, of shoulder pain in volleyball attackers. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8889124

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle-wasting disease caused by mutations in the dystrophin gene. Although dystrophin deficiency in myofiber triggers the disease's pathological changes, the degree of satellite cell (SC) dysfunction defines disease progression. Here, we have identified chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) hyperactivity as a contributing factor underlying muscular dystrophy in a dystrophin-deficient murine model of DMD. Ectopic expression of COUP-TFII in murine SCs led to Duchenne-like dystrophy in the muscles of control animals and exacerbated degenerative myopathies in dystrophin-deficient mice. COUP-TFII-overexpressing mice exhibited regenerative failure that was attributed to deficient SC proliferation and myoblast fusion. Mechanistically, we determined that COUP-TFII coordinated a regenerative program through combined regulation of multiple promyogenic factors. Furthermore, inhibition of COUP-TFII preserved SC function and counteracted the muscle weakness associated with Duchenne-like dystrophy in the murine model, suggesting that targeting COUP-TFII is a potential treatment for DMD. Together, our findings reveal a regulatory role of COUP-TFII in the development of muscular dystrophy and open up a potential therapeutic opportunity for managing disease progression in patients with DMD.

Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research. PMID:27099343

Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500–5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the DMD gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame of DMD through specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients with DMD mutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed. PMID:28280301

In overhead sports such as volleyball, baseball, or tennis shoulder problems are very common. The aim of this study was to identify features which may correlate with shoulder problems in volleyball attackers. 30 competitive volleyball attackers (mean age 25 years) were included in the study; 15 were suffering from shoulder pain and 15 had no history of shoulder pain. The results were compared with those of a control group of 15 recreational athletes without any overhead sports activities. Volleyball attackers have a different muscular and capsular pattern at the playing shoulder compared to the opposite shoulder. Their playing shoulder is depressed, the scapula lateralised, and the dorsal muscles and the posterior and inferior part of the shoulder capsule shortened. These differences were of more significance in volleyball attackers with shoulder pain than in volleyball players without shoulder pain. In contrast to recreational athletes without any overhead sports activity, there were no significant difference in the comparison of the two shoulders. The histories, clinical and sonographic findings did not reveal further typical features for volleyball attackers with shoulder pain. Muscular balance of the shoulder girdle is very important in this sport. It is therefore imperative to include adequate stretching and muscular training programme for the prevention, as well as for therapy, of shoulder pain in volleyball attackers.

The growth and unregulated structure of homeschooling creates an unknown population in regard to muscular and cardiorespiratory fitness. The purpose of this research was to compare muscular and cardiorespiratory fitness between elementary school aged homeschool and public school children. Homeschool children ages 8-11 years old (n = 75) completed the curl-up, 90° push-up, and Progressive Aerobic Capacity Endurance Run (PACER) portions of the FitnessGram to assess abdominal and upper body strength and endurance as well as cardiorespiratory fitness. Comparisons to public school children (n = 75) were made using t tests and chi-square tests. Homeschool children showed significantly lower abdominal (t(148) = -11.441, p < .001; χ(2) (1) = 35.503, p < .001) and upper body (t(148) = -3.610, p < .001; χ(2) (1) = 4.881, p = .027) strength and endurance. There were no significant differences in cardiorespiratory fitness by total PACER laps (t(108) = 0.879, p = .381) or estimated VO2max (t(70) = 1.187, p = .239; χ(2) (1) = 1.444, p = .486). Homeschool children showed significantly lower levels of both abdominal and upper body muscular fitness compared with their age and gender matched public school peers but no difference in cardiorespiratory fitness.

The origin of active predation in vertebrates is associated with the rise of three major, uniquely derived developmental characteristics of the head: (i) migratory cranial neural crest cells (CNCCs) giving rise to most skeletal skull elements; (ii) expression of Dlx genes by CNCCs in the Hox-free first pharyngeal arch (PA1); and (iii) muscularization of PA1 derivatives. Here we show that these three innovations are tightly linked. Expression of Dlx genes by CNCCs is not only necessary for head skeletogenesis, but also for the determination, differentiation, and patterning of cephalic myogenic mesoderm leading to masticatory muscle formation. In particular, inactivation of Dlx5 and Dlx6 in the mouse results in loss of jaw muscles. As Dlx5/6 are not expressed by the myogenic mesoderm, our findings imply an instructive role for Dlx5/6-positive CNCCs in muscle formation. The defect in muscularization does not result from the loss of mandibular identity observed in Dlx5/6−/− mice because masticatory muscles are still present in EdnRA−/− mutants, which display a similar jaw transformation. The genesis of jaws and their muscularization should therefore be seen as an integrated Dlx-dependent developmental process at the origin of the vertebrate head. The role of Dlx genes in defining gnathostome jaw identity could, therefore, be secondary to a more primitive function in the genesis of the oral skeletomuscular system. PMID:20534536

Muscular dystrophies refer to a group of inherited disorders characterized by progressive muscle weakness, wasting and degeneration. So far, there is no effective treatment but new gene-based therapies are currently being developed with particular noted advances in using conventional gene replacement strategies, RNA-based approaches, or cell-based gene therapy with a main focus on Duchenne muscular dystrophy (DMD). DMD is the most common and severe form of muscular dystrophy and current treatments are far from adequate. However, genetic and cell-based therapies, in particular exon skipping induced by antisense strategies, and corrective gene therapy via functionally engineered dystrophin genes hold great promise, with several clinical trials ongoing. Proof-of-concept of exon skipping has been obtained in animal models, and most recently in clinical trials; this approach represents a promising therapy for a subset of patients. In addition, gene-delivery-based strategies exist both for antisense-induced reading frame restoration, and for highly efficient delivery of functional dystrophin mini- and micro-genes to muscle fibres in vivo and muscle stem cells ex-vivo. In particular, AAV-based vectors show efficient systemic gene delivery to skeletal muscle directly in vivo, and lentivirus-based vectors show promise of combining ex vivo gene modification strategies with cell-mediated therapies.

ice and humans lacking the caveolae component polymerase I transcription release factor (PTRF, also known as cavin-1) exhibit lipo- and muscular dystrophy. Here we describe the molecular features underlying the muscle phenotype for PTRF/cavin-1 null mice. These animals had a decreased ability to exercise, and exhibited muscle hypertrophy with increased muscle fiber size and muscle mass due, in part, to constitutive activation of the Akt pathway. Their muscles were fibrotic and exhibited impaired membrane integrity accompanied by an apparent compensatory activation of the dystrophin-glycoprotein complex along with elevated expression of proteins involved in muscle repair function. Ptrf deletion also caused decreased mitochondrial function, oxygen consumption, and altered myofiber composition. Thus, in addition to compromised adipocyte-related physiology, the absence of PTRF/cavin-1 in mice caused a unique form of muscular dystrophy with a phenotype similar or identical to that seen in humans lacking this protein. Further understanding of this muscular dystrophy model will provide information relevant to the human situation and guidance for potential therapies. PMID:28289716

Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation.

Motivated by recent success in growing biohybrid material from engineered tissues on synthetic polymer films, we derive a computational simulation tool for muscular thin films in cardiac repair. In this model, the polydimethylsiloxane base layer is simulated in terms of microscopically motivated tetrahedral elements. Their behavior is characterized through a volumetric contribution and a chain contribution that explicitly accounts for the polymeric microstructure of networks of long chain molecules. Neonatal rat ventricular cardiomyocytes cultured on these polymeric films are modeled with actively contracting truss elements located on top of the sheet. The force stretch response of these trusses is motivated by the cardiomyocyte force generated during active contraction as suggested by the filament sliding theory. In contrast to existing phenomenological models, all material parameters of this novel model have a clear biophyisical interpretation. The predictive features of the model will be demonstrated through the simulation of muscular thin films. First, the set of parameters will be fitted for one particular experiment documented in the literature. This parameter set is then used to validate the model for various different experiments. Last, we give an outlook of how the proposed simulation tool could be used to virtually predict the response of multi-layered muscular thin films. These three-dimensional constructs show a tremendous regenerative potential in repair of damaged cardiac tissue. The ability to understand, tune and optimize their structural response is thus of great interest in cardiovascular tissue engineering.

Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation. PMID:24295812

Bronchiolar clearance was studied in 7 boys in the age range of 8 to 17 years, 6 with Duchenne muscular dystrophy (DMD) and 1 with spinal muscular atrophy type II (SMA-II). These boys had healthy lungs but a severely reduced muscular strength (wheelchair dependent). In 6 of the boys, clearance was studied twice, at one occasion as a control and at the other occasion following treatment with continuous positive airway pressure (CPAP). A control group of healthy adults was used. In the clearance examinations, 6-microm Teflon particles, labeled with III In was inhaled extremely slowly, 0.05 L/s. This gives a deposition mainly in the bronchioles. Lung retention was measured after 0,24,48, and 72 hours. A model for deposition of particles in the adult lung was scaled down to represent the children in this study. Deposition in various airway generations was calculated to be similar in children and adults. Also the measured retentions were similar in the boys and the adults. In the clearance experiments during CPAP treatment, there was a significantly lower retention after 72 hours (but not after 24 and 48 hours) than in the control experiments. Theresults indicate that a severe reduction of muscular strength, and thereby a reduction of mechanical movement of the lung, does not affect clearance from large and small airways. However, some effect of clearance from small airways cannot be excluded due to the short measuring period. The small but significant effect of the CPAP treatment might have potential clinical importance and suggest that bronchiolar clearance can be affected by some form of mechanical force.

We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device (LVAD) implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAins GG), in which 7 base pairs are deleted and two are inserted. While this predicts an amino acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both siblings developed progressive heart failure secondary to early onset DCM. In addition, their 7 year old nephew with delayed gross motor development, mild proximal muscle weakness, and markedly elevated serum creatine kinase (CK) level (> 13,000 IU/L) at 16 months was recently demonstrated to have the familial DMD mutation. Here we report a novel genotype of BMD with early onset DCM and progressive lethal heart failure during early adolescence. PMID:25537791

We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11 years; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAinsGG), in which seven base pairs are deleted and two are inserted. Although this predicts an amino-acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both the siblings developed progressive HF secondary to early-onset DCM. In addition, their 7-year-old nephew with delayed gross motor development, mild proximal muscle weakness and markedly elevated serum creatine kinase level (>13 000 IU l(-1)) at 16 months was recently demonstrated to have the familial DMD mutation. Here, we report a novel genotype of BMD with early-onset DCM and progressive lethal HF during early adolescence.

[Purpose] The purpose of this study was to examine whether an aerobic interval exercise using an eccentric contraction would result in skeletal muscular hypertrophy and augmentation of muscular strength in rats. [Subjects and Methods] Twenty-one female Wistar rats were used in this study. The rats were randomly divided into three groups. The control group performed no exercise. The aerobic endurance exercise group ran for 90 min. The aerobic interval exercise group ran for a total of 90 minutes in 5 minute bouts separated by 2 minute rest periods. The exercise groups ran on a downhill treadmill incline, once every three days, for a total of twenty sessions. [Results] The muscle wet weights, the muscle fiber cross-section minor axes, and the tetanus tension results of the aerobic endurance and aerobic interval exercise groups were significantly larger than those of the control group. [Conclusion] These results indicate that aerobic interval exercise may be an effective method of inducing hypertrophy and augmenting muscular strength in skeletal muscle.

Muscular dystrophy is a progressive disease of muscle weakness, muscle atrophy and cardiac dysfunction. Patients afflicted with muscular dystrophy exhibit autonomic dysfunction along with cognitive impairment, severe depression, sadness, and anxiety. Although the psychological aspects of cardiovascular disorders and stress disorders are well known, the physiological mechanism underlying this relationship is not well understood, particularly in muscular dystrophy. Therefore, the goal of this perspective is to highlight the importance of autonomic dysfunction and psychological stress disorders in the pathogenesis of muscular dystrophy. This article will for the first time—(i) outline autonomic mechanisms that are common to both psychological stress and cardiovascular disorders in muscular dystrophy; (ii) propose therapies that would improve behavioral and autonomic functions in muscular dystrophy. PMID:24523698

Men's drive for muscularity refers to the degree to which men wish to increase their muscularity. Men who are more extreme in their drive for muscularity face dangerous consequences, such as increased levels of eating pathology and use of performance-enhancing substances. The aim of this study was to predict men's drive for muscularity, and to test whether hypothesized predictive factors vary across age groups. Participants were 226 men ages 18-67. It was hypothesized that body dissatisfaction would predict men's drive for muscularity. More substantively, however, it was hypothesized that having a strong tendency to compare oneself with others would exacerbate the relationship between men's body dissatisfaction and their drive for muscularity. Results of a hierarchical multiple regression analysis supported these hypotheses. Furthermore, this exacerbating effect was present regardless of men's age. Implications for assessment, clinical practice, research, and prevention efforts are discussed.

The pursuit of muscularity is an important body image concern among boys which has been described within sociocultural models of risk for eating disorders. This study explored a sociocultural model of disordered eating in which drive for thinness and pursuit of muscularity were both pathways to disordered eating among French adolescent boys. A sample of 146 adolescents completed a questionnaire assessing drive for thinness, drive for muscularity, media-ideal internalization, appearance comparison, and sociocultural pressure. The model was a good fit to the data and both drive for thinness and the pursuit of muscularity were related to disordered eating. Furthermore, internalization and appearance comparison mediated the relationships between pressure to increase muscle and both drive for muscularity and drive for thinness. Longitudinal research could help clarify the role of the pursuit of muscularity in the development of disordered eating and extreme body shape changing behaviors.

The purpose of this study was to investigate the effects of a manual resistance training (MRT) program on muscular strength and endurance and to compare these effects with those of an identically structured weight resistance training (WRT) program. To do this, 84 healthy college students were randomly assigned to either an MRT (n = 53, mean +/- SD: age 25.6 +/- 6.0 years, height 170.1 +/- 8.1 cm, body mass 73.9 +/- 16.0 kg, and body fat 24.6 +/- 8.7%) or WRT (n = 31, mean +/- SD: age 25.5 +/- 5.2 years; height 169.6 +/- 10.1 cm, body mass 75.0 +/- 17.4 kg, and body fat 24.7 +/- 8.5%) group and engaged in a 14-week training program. Each participant's performance was assessed before and immediately after the 14-week training period. Muscular strength was assessed by the one-repetition maximum (1RM) bench press test and the 1RM squat test. Muscular endurance was recorded as the maximum number of repetitions performed with 70% of pretraining 1RM for the bench press and squat exercises. There were no significant differences between the MRT and WRT groups at baseline for muscular strength (p > 0.36) or muscular endurance (p > 0.46). Compared with baseline values, the 14-week training programs produced significant (p < 0.001) improvements in muscular strength and muscular endurance of the MRT and WRT groups. However, no significant difference was observed between the MRT and WRT groups for muscular strength (p > 0.22) or for muscular endurance (p > 0.09) after training. The improvements in muscular strength and muscular endurance after a 14-week MRT program in the present study were similar to those produced by a WRT program, and well-designed MRT exercises seem to be effective for improving muscular fitness.

The authors studied changes in development and structure of bone and muscular disorders in industrial workers of Perm area. The workers' examination considered features of physical overload during the working process. The authors revealed developmental peculiarities of bone and muscular system in various occupational groups of metallurgists, oil extractors, machinery building workers. The article shows necessity of interdisciplinary approach and observation of the workers to prevent progression of bone and muscular disorders.

Introduction: Aging leads to alterations not only within the complex subsystems of the neuro-musculo-skeletal system, but also in the coupling between them. Here, we studied how aging affects functional reorganizations that occur both within and between the behavioral and muscular levels, which must be coordinated to produce goal-directed movements. Using unimanual reciprocal Fitts' task, we examined the behavioral and muscular dynamics of older adults (74.4 ± 3.7 years) and compared them to those found for younger adults (23.2 ± 2.0 years). Methods: To achieve this objective, we manipulated the target size to trigger a phase transition in the behavioral regime and searched for concomitant signatures of a phase transition in the muscular coordination. Here, muscular coordination was derived by using the method of muscular synergy extraction. With this technique, we obtained functional muscular patterns through non-negative matrix factorization of the muscular signals followed by clustering the resulting synergies. Results: Older adults showed a phase transition in behavioral regime, although, in contrast to young participants, their kinematic profiles did not show a discontinuity. In parallel, muscular coordination displayed two typical signatures of a phase transition, that is, increased variability of coordination patterns and a reorganization of muscular synergies. Both signatures confirmed the existence of muscular reorganization in older adults, which is coupled with change in dynamical regime at behavioral level. However, relative to young adults, transition occurred at lower index of difficulty (ID) in older participants and the reorganization of muscular patterns lasted longer (over multiple IDs). Discussion: This implies that consistent changes occur in coordination processes across behavior and muscle. Furthermore, the repertoire of muscular patterns was reduced and somewhat modified for older adults, relative to young participants. This suggests that

Objective and methods Dysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed. Results and conclusions Three mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations. PMID:23243261

We present the results of the molecular genetic study of 26 patients, aged from 12 to 60 years, from 24 unrelated families with limb girdle-muscular dystrophy (LGMD) type 2A. The disease duration varied from 6 months to 30 years. The diagnosis of LGMD 2capital A, Cyrillic was confirmed by molecular genetic methods basing on the presence of a CAPN3 mutation in homozygous, compound-heterozygous and heterozygous state. The Leyden-Moebius variant that is characterized by the primary affection of muscles of pelvic girdle and shin with the gradual progression of the pathological process in shoulder girdle muscles was the most frequent in the Russian population. Tip-toe walking or difficulties in walking upstairs and running were the first symptoms reported by patients. In contrast to criteria of the European Neuromuscular Center, the characteristic symptoms of the disease were early contractures of ankle joints and pseudohypertrophy of gastrocnemius muscles. The major c.550delA mutation in the CAPN3 gene was identified in 70% of Russian patients.

The aim of this study was to characterize the muscular reservoirs of phosphorilated energetic components of athletes using 31P-MRS. The sample was formed by 14 elite athletes from the Center for High Sportive Performance (CAR, Sant Cugat del Vallés, Spain). The pattern of the phosphorilated metabolites was measured from the muscle vastus medialis by 31P-MRS. Oral supplementation of 20 g of Creatine monohydrate was given during 14 days. Two groups of athletes were formed according to their physical characteristics (weight, height, body mass index, maximum O2 uptake). The first group received a placebo (maltodextrine), while the second group received a diet of creatine supplement. The exercise was performed inside the resonance tunnel with a frequency of 60 RPM with both legs. The results showed that significant decrease occurred in phosphocreatine (PCr), inorganic phosphate (Pi) and intracellular pH after supplementation. It was concluded that the exercise performed by the long distance runners recruited in this study, detected by 31P-MRS, reduced the consumption of PCr during exercise owing to creatine supplementation diet.

A 53-year-old female with muscular symptoms and incomplete Turner's syndrome was presented. She had two sons with Duchenne type muscular dystrophy (DMD). Her muscular symptoms became apparent at age 52 years, and her elevated serum CK, EMG and pathological findings of the biopsied muscle were consistent with muscular dystrophy. Her cytogenetic analysis from the cultured lymphocytes and fibroblasts showed a 45XO/46XX/47XXX chromosome constitution. Analysis of number of Barr bodies in the muscle specimen revealed that the total number of the bodies were significantly decreased in this case than in the control muscles. The result indicated that nuclei of 45XO karyotype were evidently present in her muscle and contributed to the process of muscle fiber breakdown as a major pathogenetic factor. However, inactivation of normal X chromosome also concerned the pathologic process because there were nuclei with Barr bodies in the damaged fibers as well. Only seven cases with X chromosome mosaicism and muscular symptoms attributable to DMD gene were seen in the literature. Four of them showed rather typical clinical features of DMD, but the muscular symptoms were much milder in the remainder, and patients were still able to walk in their middle lives. It was presumed that the severity of the clinical symptoms was parallel to the ratio of 45XO karyotype in the total number of muscular nuclei.

Objective To differentiate juvenile polymyositis (PM) and muscular dystrophy, both of which may present with chronic muscle weakness and inflammation. Methods We studied 39 patients with probable or definite juvenile PM and 9 patients with muscular dystrophies who were initially misdiagnosed as having juvenile PM. Differences in demographic, clinical, and laboratory results; outcomes; and treatment responses were evaluated by Fisher’s exact and rank sum tests. Random forests classification analysis and logistic regression were performed to examine significant differences in multivariable models. Results Clinical features and serum muscle enzyme levels were similar between juvenile PM and dystrophy patients, except 89% of dystrophy patients had muscle atrophy compared with 46% of juvenile PM patients. Dystrophy patients had a longer delay to diagnosis (median 12 versus 4 months) and were less frequently hospitalized than juvenile PM patients (22% versus 74%). No dystrophy patients, but 54% of juvenile PM patients, had a myositis autoantibody. Dystrophy patients more frequently had myopathic features on muscle biopsy, including diffuse variation of myofiber size, fiber hypertrophy, and myofiber fibrosis (44–100% versus 8–53%). Juvenile PM patients more frequently had complex repetitive discharges on electromyography and a complete response to treatment with prednisone or other immunosuppressive agents than dystrophy patients (44% versus 0%). Random forests analysis revealed that the most important features in distinguishing juvenile PM from dystrophies were myositis autoantibodies, clinical muscle atrophy, and myofiber size variation on biopsy. Logistic regression confirmed muscle atrophy, myofiber fibrosis, and hospitalization as significant predictors. Conclusion Muscular dystrophy can present similarly to juvenile PM. Selected clinical and laboratory features are helpful in combination in distinguishing these conditions. PMID:23925923

This case describes the physiological maturation from ages 21 to 28 yr of the bicyclist who has now become the six-time consecutive Grand Champion of the Tour de France, at ages 27-32 yr. Maximal oxygen uptake (Vo(2 max)) in the trained state remained at approximately 6 l/min, lean body weight remained at approximately 70 kg, and maximal heart rate declined from 207 to 200 beats/min. Blood lactate threshold was typical of competitive cyclists in that it occurred at 76-85% Vo(2 max), yet maximal blood lactate concentration was remarkably low in the trained state. It appears that an 8% improvement in muscular efficiency and thus power production when cycling at a given oxygen uptake (Vo(2)) is the characteristic that improved most as this athlete matured from ages 21 to 28 yr. It is noteworthy that at age 25 yr, this champion developed advanced cancer, requiring surgeries and chemotherapy. During the months leading up to each of his Tour de France victories, he reduced body weight and body fat by 4-7 kg (i.e., approximately 7%). Therefore, over the 7-yr period, an improvement in muscular efficiency and reduced body fat contributed equally to a remarkable 18% improvement in his steady-state power per kilogram body weight when cycling at a given Vo(2) (e.g., 5 l/min). It is hypothesized that the improved muscular efficiency probably reflects changes in muscle myosin type stimulated from years of training intensely for 3-6 h on most days.

BACKGROUND: The autosomal recessive limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous muscle diseases characterised by progressive proximal limb muscle weakness. Six different loci have been mapped and pathogenetic mutations in the genes encoding the sarcoglycan complex components (alpha-, beta-, gamma-, and delta-sarcoglycan) have been documented. LGMD patients affected with primary "sarcoglycanopathies" are classified as LGMD2D, 2E, 2C, and 2F, respectively. METHODS: A geographical area in north east Italy (2,319,147 inhabitants) was selected for a genetic epidemiological study on primary sarcoglycanopathies. Within the period 1982 to 1996, all patients living in this region and diagnosed with muscular dystrophy were seen at our centre. Immunohistochemical and immunoblot screening for alpha-sarcoglycan protein deficiency was performed on all muscle biopsies from patients with a progressive muscular dystrophy of unknown aetiology and normal dystrophin. Sarcoglycan mutation analyses were conducted on all patient muscle biopsies shown to have complete or partial absence of alpha-sarcoglycan immunostaining or a decreased quantity of alpha-sarcoglycan protein on immunoblotting. RESULTS: Two hundred and four patient muscle biopsies were screened for alpha-sarcoglycan protein deficiency and 18 biopsies showed a deficiency. Pathogenetic mutations involving one gene for sarcoglycan complex components were identified in 13 patients: alpha-sarcoglycan in seven, beta-sarcoglycan in two, gamma-sarcoglycan in four, and none in the delta-sarcoglycan gene. The overall prevalence of primary sarcoglycanopathies, as of 31 December 1996, was estimated to be 5.6 x 10(-6) inhabitants. CONCLUSION: The prevalence rate estimated in this study is the first to be obtained after biochemical and molecular genetic screening for sarcoglycan defects. PMID:9429136

For marine mammals, the ability to tolerate apnea and make extended dives is a defining adaptive trait, facilitating the exploitation of marine food resources. Elevated levels of myoglobin within the muscles are a consistent hallmark of this trait, allowing oxygen collected at the surface to be stored in the muscles and subsequently used to support extended dives. In mysticetes, the largest of marine predators, details on muscular myoglobin levels are limited. The developmental trajectory of muscular myoglobin stores has yet to be documented and any physiological links between early behavior and the development of muscular myoglobin stores remain unknown. In this study, we used muscle tissue samples from stranded mysticetes to investigate these issues. Samples from three different age cohorts and three species of mysticetes were included (total sample size = 18). Results indicate that in mysticete calves, muscle myoglobin stores comprise only a small percentage (17–23%) of conspecific adult myoglobin complements. Development of elevated myoglobin levels is protracted over the course of extended maturation in mysticetes. Additionally, comparisons of myoglobin levels between and within muscles, along with details of interspecific differences in rates of accumulation of myoglobin in very young mysticetes, suggest that levels of exercise may influence the rate of development of myoglobin stores in young mysticetes. This new information infers a close interplay between the physiology, ontogeny and early life history of young mysticetes and provides new insight into the pressures that may shape adaptive strategies in migratory mysticetes. Furthermore, the study highlights the vulnerability of specific age cohorts to impending changes in the availability of foraging habitat and marine resources. PMID:26788728

This study aimed to investigate the effects of wearing a compression garment (CG) for 24 h on changes in muscular strength and blood parameters over time after resistance exercise. Nine trained men conducted resistance exercises (10 repetitions of 3-5 sets at 70% of one-repetition maximum (1RM) for nine exercises) in two trials, wearing either a CG or a normal garment (CON) for 24 h after exercise. Recovery of muscular strength, blood parameters, muscle soreness, and upper arm and thigh circumference were compared between the trials. Both trials showed decreases in maximal strength after the exercise (P < 0.05). However, the CG trial showed faster recovery of one-repetition maximum for the chest press from 3 to 8 h after exercise (P < 0.05). Recovery of maximal knee extension strength was also improved in the CG trial 24 h after exercise (P < 0.05). The CG trial was associated with lower muscle soreness and subjective fatigue scores the following morning (P < 0.05). The upper arm and thigh circumferences were significantly higher during the recovery period in the CON trial, whereas no change was observed in the CG trial. Blood lactate, insulin like growth factor-1, free testosterone, myoglobin, creatine kinase, interleukin 6, and interleukin 1 receptor antagonist concentrations for 24 h after exercise were similar in both trials. Wearing a CG after resistance exercise facilitates the recovery of muscular strength. Recovery for upper body muscles significantly improved within 3-8 h after exercise. However, facilitation of recovery of lower limb muscles by wearing the CG took a longer time.

Despite the widespread use of and acceptance of muscular fitness field tests in national youth fitness test batteries, little is known about how these field tests compare to 1 repetition maximum (1RM) strength in children. Therefore, the aim of this study was to characterize and identify correlates of muscular strength in children 7 to 12 years of age. Ninety children (39 girls and 51 boys) between the ages of 6.7 and 12.3 years volunteered to participate in this study. Children were tested on 1RM chest press (CP) strength, 1RM leg press (LP) strength, handgrip strength, vertical jump, long jump, sit and reach flexibility, and height and weight (used to determine body mass index [BMI]). For the combined sample, LP 1RM ranged from 75% to 363% of body weight and CP 1RM ranged from 25% to 103% of body weight. Multiple regression analyses predicting LP 1RM showed that BMI and long jump were significant (R = 44.4% with age and gender not significant) and BMI and vertical jump were significant (R = 40.8% with age and gender not significant). Multiple regression analyses predicting CP 1RM showed that BMI and handgrip strength were significant (R = 58.6% with age and gender not significant). Age and gender alone accounted for 4.6% (not significant) of the variation in LP 1RM and 15.4% (significant) in CP 1RM. In summary, these data indicate that BMI, handgrip strength, long jump, and vertical jump relate to 1RM strength in children and therefore may be useful for assessing muscular fitness in youths.

Study Objectives: Reduced mobility during sleep characterizes a variety of movement disorders and neuromuscular diseases. Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy in the general population, and people with FSHD have poor sleep quality. The aims of the present study were to evaluate nocturnal motor activity in patients with FSHD by means of videopolysomnography and to verify whether activity was associated with modifications in sleep structure. Methods: We enrolled 32 adult patients affected by genetically confirmed FSHD (18 women and 14 men, mean age 45.1 ± 13.4 years) and 32 matched control subjects, (18 women and 14 men, mean age 45.5 ± 11.4 years). Major body movements (MBM) were scored in videopolygraphic recordings in accordance with established criteria. An MBM index was calculated (number of MBM per hour of sleep). Results: The FSHD group showed a decrease in the MBM index (FSHD: 1.2 ± 1.1; control subjects: 2.3 ± 1.2, analysis of variance F = 13.672; p = 0.008). The sleep pattern of patients with FSHD, as compared with that of controls, was characterized by longer sleep latencies, shorter sleep durations, an increased percentage of wake during sleep, and a decreased percentage of rapid eye movement sleep. In the patient group, the MBM index was inversely correlated with severity of disease (Spearman test: r30 = −0.387; p < 0.05). Conclusions: The present findings suggest that patients with FSHD have a reduced number of nocturnal movements, which is related to disease severity. Reduced movement in bed may contribute to the sleep modifications observed in these patients. Citation: Marca GD; Frusciante R; Dittoni S; Vollono C; Losurdo A; Testani E; Scarano E; Colicchio S; Iannaccone E; Tonali PA; Ricci E. Decreased nocturnal movements in patients with facioscapulohumeral muscular dystrophy. J Clin Sleep Med 2010;6(3):276-280. PMID:20572422

For marine mammals, the ability to tolerate apnea and make extended dives is a defining adaptive trait, facilitating the exploitation of marine food resources. Elevated levels of myoglobin within the muscles are a consistent hallmark of this trait, allowing oxygen collected at the surface to be stored in the muscles and subsequently used to support extended dives. In mysticetes, the largest of marine predators, details on muscular myoglobin levels are limited. The developmental trajectory of muscular myoglobin stores has yet to be documented and any physiological links between early behavior and the development of muscular myoglobin stores remain unknown. In this study, we used muscle tissue samples from stranded mysticetes to investigate these issues. Samples from three different age cohorts and three species of mysticetes were included (total sample size = 18). Results indicate that in mysticete calves, muscle myoglobin stores comprise only a small percentage (17-23%) of conspecific adult myoglobin complements. Development of elevated myoglobin levels is protracted over the course of extended maturation in mysticetes. Additionally, comparisons of myoglobin levels between and within muscles, along with details of interspecific differences in rates of accumulation of myoglobin in very young mysticetes, suggest that levels of exercise may influence the rate of development of myoglobin stores in young mysticetes. This new information infers a close interplay between the physiology, ontogeny and early life history of young mysticetes and provides new insight into the pressures that may shape adaptive strategies in migratory mysticetes. Furthermore, the study highlights the vulnerability of specific age cohorts to impending changes in the availability of foraging habitat and marine resources.

MicroRNAs (miRNAs) are endogenous small RNAs of 18-23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we explored whether miRNA expression profiling of various muscle cells may be useful for the diagnosis of various diseases involving muscle necrosis. miRNA expression profiling was assessed by miRNA array and real-time reverse-transcriptase polymerase chain reaction by using a reverse primer of a stem loop structure. Profiling of various muscle cells of mouse, including cardiac muscles, skeletal muscles, and vascular and visceral smooth muscles, indicated that profiling of miR-1, miR-133a, miR-133b, miR-145, miR-206, miR-208a, miR-208b, and miR499 were adequate to discriminate muscle cells. miR-145 was remarkably highly expressed in smooth muscles. miR-208a and miR-499 were highly expressed in cardiomyocytes. miR-133a was highly expressed in fast-twitch skeletal muscles. miR-206 and miR-208b were expressed in the slow-twitch skeletal muscles, and they can likely discriminate fast- and slow-twitch types of skeletal muscle cells. We observed that brown fat adipose cells had an miRNA expression profile very similar to those of skeletal muscle cells in the mouse. Plasma concentrations of miR-133a and miR-145 were extremely useful in diagnosing skeletal muscle necrosis in a mouse model of Duchenne muscular dystrophy and colon smooth muscle necrosis in a rat ischemic colitis model, respectively. In the present study, we investigated the miRNA expression profiles of various muscular tissues. Our results suggest that expression profiling would be useful for the diagnosis of various diseases such as muscular necrosis.

Halofuginone has been shown to prevent fibrosis via the transforming growth factor-β/Smad3 pathway in muscular dystrophies. We hypothesized that halofuginone would reduce apoptosis--the presumed cause of satellite-cell depletion during muscle degradation-in the mdx mouse model of Duchenne muscular dystrophy. Six-week-old mdx mouse diaphragm exhibited fourfold higher numbers of apoptotic nuclei compared with wild-type mice as determined by a TUNEL assay. Apoptotic nuclei were found in macrophages and in Pax7-expressing cells; some were located in centrally-nucleated regenerating myofibers. Halofuginone treatment of mdx mice reduced the apoptotic nuclei number in the diaphragm, together with reduction in Bax and induction in Bcl2 levels in myofibers isolated from these mice. A similar effect was observed when halofuginone was added to cultured myofibers. No apparent effect of halofuginone was observed in wild-type mice. Inhibition of apoptosis or staurosporine-induced apoptosis by halofuginone in mdx primary myoblasts and C2 myogenic cell line, respectively, was reflected by less pyknotic/apoptotic cells and reduced Bax expression. This reduction was reversed by a phosphinositide-3-kinase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase inhibitors, suggesting involvement of these pathways in mediating halofuginone's effects on apoptosis. Halofuginone increased apoptosis in α smooth muscle actin- and prolyl 4-hydroxylase β-expressing cells in mdx diaphragm and in myofibroblasts, the major source of extracellular matrix. The data suggest an additional mechanism by which halofuginone improves muscle pathology and function in muscular dystrophies.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common myopathy. It is characterized by progressive descendent involvement of facial, shoulder girdle, truncal and lower extremities muscles. FSHD locus was mapped on the terminal part of the long arm of chromosome 4 (4q35). The disease is caused by a deletion of an integral number of tandem D4Z4 repeats and dimension of the pathological fragments < or = 38kb. Prenatal diagnosis of FSHD is possible but it is potentially difficult because of the big amount and high quality of DNA required. Hereby we describe the first prenatal tests performed for a Bulgarian family.

Duchenne muscular dystrophy is a progressive disease with loss of ambulation at around 9-10 years of age, followed, if untreated, by development of scoliosis, respiratory insufficiency, and death in the second decade of life. This review highlights the natural history of the disease, in particular, with regard to the development of the spinal deformity and how this complication has been modified by surgical interventions and overall by corticosteroid treatment. The beneficial effect of corticosteroids may have also an impact on the clinical trial design of the new emerging causative therapies. PMID:27382620

Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease which affects specific muscles. No pharmacological treatments are currently available for OPMD. In recent years, genetically tractable models of OPMD – Drosophila and Caenorhabditis elegans – have been generated. Although these models have not yet been used for large-scale primary drug screening, they have been very useful in candidate approaches for the identification of potential therapeutic compounds for OPMD. In this brief review, we summarize the data that validated active molecules for OPMD in animal models including Drosophila, C. elegans and mouse.

An account of the authors' experience in strength measurement using a hand-held dynamometer in 16 patients with Duchenne muscular dystrophy (DMD) is given. A rapid decrease of knee extension strength was observed, between 6 and 8 years of age, analysing among patients of different ages. At the same time loss of the ability to walk has occurred. An unexplainable increase in strength was observed in two patients examined in a six month interval. A short review of the literature is given and the conclusion of the importance on the wider use of the instrument.

Cell-based therapy for muscular dystrophies was initiated in humans after promising results obtained in murine models. Early trials failed to show substantial clinical benefit, sending researchers back to the bench, which led to the discovery of many hurdles as well as many new venues to optimize this therapeutic strategy. In this review we summarize progress in preclinical cell therapy approaches, with a special emphasis on human cells potentially attractive for human clinical trials. Future perspectives for cell therapy in skeletal muscle are discussed, including the perspective of combined therapeutic approaches.

Minipolymyoclonus has been described in both anterior horn cell disorders and central nervous system degenerative conditions. While its etiology remains unclear and speculative, a central generator has been previously proposed. We describe a case of bulbospinal muscular atrophy (Kennedy's disease), where minipolymyoclonus-like movements corresponded to fasciculations in neurophysiological studies. Our novel finding suggests that the etiologies of minipolymyoclonus in central and peripheral nervous system disorders are distinct, despite outward clinical similarity. The term “minipolyfasciculations” may be more reflective of the underlying process causing minipolymyoclonus-like movements in lower motor neuron disorders. PMID:26019432

The Canadian medical staff at the 1976 Olympic Games found that muscular low back pain was a common problem among the athletes. The problem had usually developed during training as a result of neglect of certain anatomic areas, particularly the abdominal region. A five-point treatment and prevention program was used with good results. It included (a) relief of spasm and pain, (b) stretching, (c) exercise, (d) alteration of the training program and (e) education to prevent future problems or worsening of the present problem.

This is a report on eight cases of a rare congenital malformation in the upper extremity, consisting of a unilateral muscular hyperplasia. In addition to the hand, all segments of the upper extremity may be affected. The hyperplasia is always unilateral, preferably on the right hand side, in combination with accessory muscles. Hereditary dependence or association with other malformations has not been observed. Six of eight patients were male. Shoulder and arm function were normal in all cases. Ulnar drift of the fingers in the metacarpophalangeal joints (six of eight patients), flexion contractures of the metacarpophalangeal joints (six of eight patients) and extension contractures of the wrist (three of eight patients) to various degrees were seen. A prominence of the second and third metacarpal head with an enlarged space between them gave the affected hands a very typical appearance (six of eight patients). Deformities and functional limitations requiring surgical treatment were present in six patients. In all cases, accessory muscles were found intraoperatively and resected. The macroscopic and microscopic appearance of the muscle specimen did not differ from normal muscular tissue. In all cases, additional procedures were necessary to improve the overall function. Nevertheless, the reconstructive efforts did not lead to an entirely normal hand function or appearance. The malformation we describe can clearly be distinguished from other malformations such as arthrogryposis multiplex congenita, Freeman-Sheldon syndrome or macrodactyly. Up to now, only two other reports were found in the literature showing characteristics similar to those in our own cases. Four similar cases were observed by Benatar. From a pathomechanical point of view, a disturbance in the muscular balance seems to cause the deformities and functional limitations. This imbalance could be related to accessory muscles which are not opposed by defined antagonists or to an unbalanced hyperplasia of

Duchenne muscular dystrophy is an X-linked recessive disorder caused by the absence of dystrophin. Heart involvement is a classical complication in this disease and leads progressively to heart failure. Detecting latent myocardial involvement is essential in this disease because early use of drugs like angiotensin-converting enzyme inhibitors may delay the progression of heart disease. Myocardial strain imaging is an application of the tissue Doppler imaging. By assessing regional myocardial function, this tool might help clinicians to detect latent myocardial involvement in DMD patients.

Sarcocysts of an unidentified Sarcocystis species were found in sections of skeletal muscles of a black bear (Ursus americanus) from North Carolina. Two sarcocysts in a section measured 45 x 37.5 microm and 67.5 x 50 microm and had a thin (<2 microm) sarcocyst wall. The villar protrusions on the cyst wall were up to 2 microm long and up to 0.7 microm wide. The bradyzoites were approximately 6 X 2.5 microm in size. This is the first report of muscular Sarcocystis in a bear.

Currently, there is no cure for the treatment of spinal muscular atrophy (SMA). Based on the available clinical and molecular findings, different therapeutic strategies were tested in vitro and in vivo and clinical trials are ongoing. The main therapeutic direction is focused on the enhancement of SMN expression by increasing the full-length (fl) SMN2 transcript levels, preventing the SMN exon 7 from skipping or from protein stabilizing. In addition, the action of neurotrophic, neuroprotective or anabolic agents is tested and stem cell and gene therapy approaches are in a promising development.

This study aims to evaluate the acute effects of different stretching exercises on muscular endurance in men, in terms of the number of sets, set duration, and type of stretching. Two experiments were conducted; in the first one (E1), the subjects (n = 19) were evaluated to test the effect on the number of sets, and, in the second one (E2), the subjects (n = 15) were tested for the effect of set duration and type of stretching. After a warm-up of 10-15 repetitions of a bench press (BP) with submaximal effort, a one-repetition maximum (1RM) test was applied. For E1, BP endurance was evaluated after static stretching comprising one set of 20 seconds (1 x 20), two sets of 20 seconds (2 x 20), and three sets of 20 seconds (3 x 20). For E2, BP endurance was evaluated after static stretching comprising one set of 20 seconds (1 x 20), one set of 40 seconds (1 x 40), and proprioceptive neuromuscular facilitation (PNF) stretching. All tests were performed 48-72 hours apart, at which time the muscular endurance was assessed through the maximal number of repetitions (NR) of BP at 85% of 1RM until fatigue. The NR and the overload volume (OV) were compared among tests through repeated-measures analysis of variance. No significant effect of the number of sets on muscular endurance was observed because no statistically significant difference was found when comparing all stretching exercises of E1 in terms of NS (p = 0.5377) and OV (p = 0.5723). However, significant reductions were obtained in the set duration and PNF on NR (p < 0.0001) and OV (p < 0.0001), as observed in E2. The results suggest that a stretching protocol can influence BP endurance, whereas a decrease in endurance is suggested to be attributable to set duration and PNF. On the other hand, a low volume of static stretching does not seem to have a significant effect on muscular endurance.

The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of whole-exome sequencing and next-generation sequencing-based gene panels. In this study, we identify a deep intronic mutation in the DMD gene in a patient with muscular dystrophy using both conventional and RNAseq-based transcriptome analyses. The implications of our data are that noncoding mutations likely comprise an important source of unresolved genetic disease and that RNAseq is a powerful platform for detecting such mutations.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder that is characterized by degeneration of the anterior horn cells, leading to symmetrical muscle weakness and wasting of voluntary muscles. SMA affects 1/10,000 live births and has an estimated carrier frequency of 1/40. Affected individuals are classified into three groups, depending on the age at onset and progression of the disease, and all three forms of SMA are linked to the same set of genetic markers in the chromosome. 15 refs., 3 figs.

This is a systematic review and evaluation of the current evidence on the association between muscular endurance (ME) and/or muscular strength (MS) and musculoskeletal injury (MSK-I) risk in military and civilian populations. MEDLINE, EBSCO, EMBASE, and the Defense Technical Information Center were searched for original studies published from 1970 through 2015 that examined associations between physical fitness (ME and MS) and MSK-I in military or civilian populations. Methodological quality and strength of the evidence were determined following criteria adapted from previously published systematic reviews. Forty-five of 4,229 citations met our inclusion criteria. Although results for some tests did vary by sex, taken together, our primary findings indicate there is 1) strong evidence that poor performance on a push-up test is associated with MSK-I risk; 2) moderate evidence that poor performance on sit-up test is associated with MSK-I risk; 3) moderate evidence that isokinetic ankle and knee flexion strength, and isometric strength assessments at the back, elbow, or knee are associated with MSK-I risk; and 4) limited evidence that poor performance on a pull-up test and isotonic assessments of muscular strength are associated with MSK-I. Several measures of ME/MS are moderately or strongly associated with risk for MSK-I, but additional research is needed to identify and recommend specific assessments of ME/MS that predict MSK-I in both males and females. Future studies should also consider measures of ME and MS as a function of upper body, lower body, and core strength, and their potential association with specific, rather than general, MSK-I.

Versatility of CRISPR/Cas9-based platforms makes them promising tools for the correction of diverse genetic/epigenetic disorders. Here we contrast the use of these genome editing tools in two myopathies with very different molecular origins: Duchenne muscular dystrophy, a monogenetic disease, and facioscapulohumeral muscular dystrophy, an epigenetic disorder with unique therapeutic challenges.

Discussed are personality aspects of Duchenne or pseudohypertrophic muscular dystrophy, a progressive wasting of muscular tissue, which afflicts only boys, and usually has its noticeable onset before the age of 6 years; and described is the development of three male dystrophic siblings. (DB)

Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance,…

Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the…

Discussed are personality aspects of Duchenne or pseudohypertrophic muscular dystrophy, a progressive wasting of muscular tissue, which afflicts only boys, and usually has its noticeable onset before the age of 6 years; and described is the development of three male dystrophic siblings. (DB)

Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the…

The primary purpose of this study was to determine if muscular endurance is affected by referenced waist circumference groupings, independent of body mass and subcutaneous abdominal fat, in women. This study also explored whether selected body composition measures were associated with muscular endurance. Eighty-four women were measured for height,…

Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

The effects of three resistance training programs on male college students' muscular strength and absolute and relative muscular endurance were investigated. Results show that human skeletal muscle makes both general and specific adaptations to a training stimulus, and that the balance of these adaptations is to some extent dependent upon the…

The primary purpose of this study was to determine if muscular endurance is affected by referenced waist circumference groupings, independent of body mass and subcutaneous abdominal fat, in women. This study also explored whether selected body composition measures were associated with muscular endurance. Eighty-four women were measured for height,…

The effects of three resistance training programs on male college students' muscular strength and absolute and relative muscular endurance were investigated. Results show that human skeletal muscle makes both general and specific adaptations to a training stimulus, and that the balance of these adaptations is to some extent dependent upon the…

The purpose of this study was to determine the effects of manual negative accentuated resistance on strength and/or muscular endurance. Three strength and/or muscular endurance tests were administered to male and female physical education majors enrolled in a required exercise class at the beginning and end of the semester. Push-ups, chin-ups, and…

Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients. Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy. Results: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes. Conclusions: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions. PMID:27281536

The secondary loss of neuronal nitric oxide synthase (nNOS) that occurs in dystrophic muscle is the basis of numerous, complex and interacting features of the dystrophic pathology that affect not only muscle itself, but also influence the interaction of muscle with other tissues. Many mechanisms through which nNOS deficiency contributes to misregulation of muscle development, blood flow, fatigue, inflammation and fibrosis in dystrophic muscle have been identified, suggesting that normalization in NO production could greatly attenuate diverse aspects of the pathology of muscular dystrophy through multiple regulatory pathways. However, the relative importance of the loss of nNOS from the sarcolemma versus the importance of loss of total nNOS from dystrophic muscle remains unknown. Although most current evidence indicates that nNOS localization at the sarcolemma is not required to achieve NO-mediated reductions of pathology in muscular dystrophy, the question remains open concerning whether membrane localization would provide a more efficient rescue from features of the dystrophic phenotype. PMID:25194047

The regenerative potential of muscle tissue relies mostly on satellite cells situated between the muscular basal membrane and the sarcolemma. The regeneration of muscle tissue comprises proliferation, the propagation of satellite cells, and their subsequent differentiation with the expression of multiple muscle-specific proteins. However, in Duchenne muscular dystrophy (DMD), regeneration cannot compensate for the loss of muscle tissue. To examine the regenerative potential in DMD, satellite cell nuclei number and markers of differentiation in DMD muscle from various disease states were compared with control muscle. Differentiation of satellite cells is characterized by the helix-loop-helix factor myogenin, which is never co-expressed with Pax7, whereas MyoD1 and Myf5 are co-expressed with Pax7, with Myf5 being present even in muscle of controls. The results indicate that satellite cell number is elevated in DMD in comparison with control muscle, even in advanced stages of dystrophy, suggesting that exhaustion of satellite cells is not the primary cause for failed regeneration. The expression of myogenin is correlated neither with fibrosis nor with age. We suggest variable factors influencing the differentiation of satellite cells in DMD.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that is not due to a classical mutation within a protein-coding gene. Instead, almost all FSHD patients carry deletions of an integral number of tandem 3.3-kilobase repeat units, termed D4Z4, located on chromosome 4q35 (ref. 3). D4Z4 contains a transcriptional silencer whose deletion leads to inappropriate overexpression in FSHD skeletal muscle of 4q35 genes located upstream of D4Z4 (ref. 4). To identify the gene responsible for FSHD pathogenesis, we generated transgenic mice selectively overexpressing in skeletal muscle the 4q35 genes FRG1, FRG2 or ANT1. We find that FRG1 transgenic mice develop a muscular dystrophy with features characteristic of the human disease; by contrast, FRG2 and ANT1 transgenic mice seem normal. FRG1 is a nuclear protein and several lines of evidence suggest it is involved in pre-messenger RNA splicing. We find that in muscle of FRG1 transgenic mice and FSHD patients, specific pre-mRNAs undergo aberrant alternative splicing. Collectively, our results suggest that FSHD results from inappropriate overexpression of FRG1 in skeletal muscle, which leads to abnormal alternative splicing of specific pre-mRNAs.

Spinal muscular atrophy (SMA) is the most frequent genetic cause of death in infants and toddlers. All cases of spinal muscular atrophy result from reductions in levels of the survival motor neuron (SMN) protein, and so SMN upregulation is a focus of many preclinical and clinical studies. We examine four issues that may be important in planning for therapeutic success. First, neuromuscular phenotypes in the SMNΔ7 mouse model closely match those in human patients but peripheral disease manifestations differ, suggesting that endpoints other than mouse lifespan may be more useful in predicting clinical outcome. Second, SMN plays important roles in multiple central and peripheral cell types, not just motor neurons, and it remains unclear which of these cell types need to be targeted therapeutically. Third, should SMN-restoration therapy not be effective in all patients, blocking molecular changes downstream of SMN reduction may confer significant benefit, making it important to evaluate therapeutic targets other than SMN. Lastly, for patients whose disease progression is slowed, but who retain significant motor dysfunction, additional approaches used to enhance regeneration of the neuromuscular system may be of value. PMID:25705387

Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus. PMID:25116414

In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

A six-month-old male entire Norfolk terrier was presented with a 3-month history of poor development, reluctance to exercise and progressive and diffuse muscle atrophy. Serum creatine kinase concentration was markedly elevated. Magnetic resonance imaging of the epaxial muscles revealed asymmetrical streaky signal changes aligned within the muscle fibres (hyperintense on T2-weighted images and short-tau inversion recovery with moderate contrast enhancement on T1-weighted images). Electromyography revealed pseudomyotonic discharges and fibrillation potentials localised at the level of the supraspinatus, epaxial muscles and tibial cranialis muscles. Muscle biopsy results were consistent with dystrophin-deficient muscular dystrophy. The dog remained stable 7 months after diagnosis with coenzyme Q10 and l-carnitine; however after that time, there was a marked deterioration and the owners elected euthanasia. This case report describes the clinical presentation, magnetic resonance imaging, electrodiagnostic and histopathological findings with immunohistochemical analysis in a Norfolk terrier with confirmed dystrophin-deficient muscular dystrophy, which has not been previously described in this breed.

The load on the hip joint and activation of the gluteus maximus, hamstrings, adductor magnus and rectus femoris muscles during rising exercises including different adaptive adjustments were investigated in nine healthy subjects. The joint load was calculated from forces recorded with a force-measuring platform and pictures on cine-film. Levels of muscular activity were recorded with rectified, low-pass filtered, time-averaged and normalized EMGs. The loading moment about the hip joint was about 45 Nm during the initial part of the rising exercise, decreasing with smaller hip angle. Increase of the backward inclination of the trunk increased the load moment, which was maintained at about the same level during the rising exercise. Two adaptive adjustments lowered the joint load: foot position further backward and reduced resistance from the device. Foot position further forward increased the joint load. The levels of muscular activity in the hip extensors were low to medium and were slightly increased by posterior foot position and increased resistance from the device. Increased backward trunk inclination increased the activity in the final part of the rising exercise.

Extraocular muscles are generally considered to be spared in Duchenne Muscular Dystrophy (DMD). However, this assumption is based mainly on clinical observations, as systematic eye movement recordings have been performed in a very limited number of cases. Our goal was to analyze several saccade parameters in a higher number of cases, in order to reveal a possible ocular-motor impairment in DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy male subjects of comparable age as controls. We used the electrooculographic (EOG) technique coupled with advanced digital signal processing; saccade duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak velocity) were measured. The DMD group showed saccades with significantly longer duration and lower velocity, with respect to controls; these differences were accounted for mainly by the largest movements, whereas there were no significant differences at the smallest eccentricity tested (3 deg). Neither amplitude nor K factor were significantly different from controls for any of the eccentricities tested. To our knowledge. this is the first study to suggest significant impairment of eye movements in Duchenne muscular dystrophy.

Temporomandibular disorders (TMD) refer to a group of clinical picture affecting the masticatory muscles and temporomandibular joint that are characterized by muscular or joint pain, dysfunction (limited or altered functions) and joint noises, as well as other associated symptoms, such as tension headaches, otalgia, dizziness, tinnitus, and others. Fibromyalgia (FM) is a syndrome of unknown etiology involving generalized chronic pain accompanied, in a high percentage of cases, by other symptoms such as asthenia, anxiety, depression, sleep disturbances, and other less frequent symptoms, such as temporomandibular disorders (TMD). Data were compiled by two experienced examiners following a specific form. An electronic search was carried out in the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and SCOPUS electronic databases (up to April 2016, unrestricted by date or language). Comparative clinical studies with patients with both clinical pictures involving the study of pathogenic processes. Fibromyalgia and temporomandibular disorders with muscle pain both have profiles that affect the muscular system and therefore share many epidemiological, clinical, and physiopathological symptoms. Because of this, we are led to think that there is, if not a common etiology, at least a common pathogenesis. This article revises the physiopathological processes of both clinical pictures in an attempt to determine their similarities and likenesses. This would undoubtedly help in providing a better therapeutic approach.

In order to analyze the evolution of cardiomyopathy in progressive muscular dystrophies, thirty-three patients (17 with Duchenne type, 11 with Becker type and 5 with the autosomal recessive type dystrophy) were studied retrospectively. Cardiac and systemic follow-up every 3-6 months was made in 29 patients. The electrocardiogram was the first test that became altered, followed by the echocardiogram and thoracic radiograph and finally heart failure manifestations. There was a direct correlation between age and the appearance of abnormal cardiac tests. Electrocardiographic alterations, in patients who were less than 12.5 years of age, were significantly more frequent in the group with Duchenne dystrophy that in the no-Duchenne group. In regards to the appearance of the echocardiographic and radiographic abnormalities, there were no significant differences between the two groups. However, we have noticed a trend towards a more frequent and earlier presentation of these abnormalities in the Duchenne's muscular dystrophy than in the no-Duchenne group.

The branch from the median nerve to the thenar muscles has a proximal and lateral (recurrent) course and is vulnerable to lesions that affect these muscles. Because of its anatomical-clinical importance, this branch was studied in 60 palmar regions from 30 cadavers of adult individuals of both sexes, aged between 23 and 77 y. It arose from the lateral branch of the median nerve in 83.3% of the cases. Its origin was distal to the flexor retinaculum in 48.3%, at the distal margin of the retinaculum in 31.6%, in the carpal tunnel in 18.3% and proximal to the retinaculum in 1.7%; it pierced the retinaculum in 15%. The point of recurrence of the branch was localised topographically to 34.6 +/- 3.6 mm from the distal wrist crease; the angle between its recurrent course and the longitudinal axis of the hand averaged 66.8 degrees. In 50% of the cases the muscular branch innervated abductor pollicis brevis (APB), opponens pollicis (OP) and the superficial head of flexor pollicis brevis (FPB), in 40% it supplied only APB and OP, and in 10% a short muscular branch gave rise to independent branches in the palm and which supplied APB, OP and the superficial head of FPB. The so called "accessory thenar branch' was found in 38.3%. Images Fig. 1 Fig. 2 PMID:8886966

The interaction of the crural fascia with muscular compartments and surrounding tissues can be at the origin of different pathologies, such as compartment syndrome. This pathology consists in the onset of excessive intracompartmental pressure, which can have serious consequences for the patient, compromising blood circulation. The investigation of compartment syndrome etiology also takes into account the alteration of crural fascia mechanical properties as a cause of the syndrome, where the fascial stiffening would result in the rise of intracompartmental pressure. This work presents a computational approach toward evaluating some biomechanical aspects of the problem, within the context of a more global viewpoint. Finite element analyses of the interaction phenomena of the crural fascia with adjacent regions are reported here. This study includes the effects of a fascial stiffness increase along the proximal-distal direction and their possible clinical implications. Furthermore, the relationship between different pre-strain levels of the crural fascia in the proximal-distal direction and the rise of internal pressure in muscular compartments are considered. The numerical analyses can clarify which aspects could be directly implied in the rise of compartment syndrome, leading to greater insight into muscle-fascia mechanical phenomena, as well as promoting experimental investigation and clinical analysis of the syndrome.

The identification of the Duchenne muscular dystrophy gene and protein in the late 1980s led to high hopes of rapid translation to molecular therapeutics. These hopes were fueled by early reports of delivering new functional genes to dystrophic muscle in mouse models using gene therapy and stem cell transplantation. However, significant barriers have thwarted translation of these approaches to true therapies, including insufficient therapeutic material (eg, cells and viral vectors), challenges in systemic delivery, and immunological hurdles. An alternative approach is to repair the patient's own gene. Two innovative small-molecule approaches have emerged as front-line molecular therapeutics: exon skipping and stop codon read through. Both approaches are in human clinical trials and aim to coax dystrophin protein production from otherwise inactive mutant genes. In the clinically severe dog model of Duchenne muscular dystrophy, the exon-skipping approach recently improved multiple functional outcomes. We discuss the status of these two methods aimed at inducing de novo dystrophin production from mutant genes and review implications for other disorders. PMID:21703390

We investigated the cortico-muscular coherence in a patient with posturally induced cortically originating negative myoclonus. We recorded simultaneously 50 channels EEG and EMG from quadriceps and biceps femoris muscles of the left upper leg. Three experimental conditions were investigated with the patient in a seated position: (i) recording during rest (Rest), (ii) recording while the patient had to hold his left leg horizontally stretched out (Postural), and (iii) recording while the patient had to hold his left leg horizontally stretched out against a vertical force (Postural against force). Coherence, phase difference and cumulant density were computed as indicators for cortico-muscular coupling. The cortical component preceding the silent period was shown by averaging and was reconstructed. During postural and postural against force conditions, the EEG over the vertex was significantly coherent with EMG, in alpha (7-15 Hz) and beta range (15-30 Hz). The strongest coherence peak was at 21 Hz. No high-frequency coherence was observed. The phase difference and the cumulant density estimate corresponded to a 32 ms time lag between motor cortex and muscles, with EEG leading. The broadening of the coherence spectrum at which the motor cortex drives the muscles together with the excessive coherence levels and the giant SEP could reflect the hyperexcitability of the sensorimotor cortex. The frequency content of the coherence may be characteristic for this type of myoclonus. The results lend support to the view that the frequency analysis may have some diagnostic potential in cortical myoclonus.

Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

This study examined the thigh muscularity and strength capability in early adolescent soccer players. The cross-sectional areas (CSAs) of the thigh muscles and dynamic strength during knee extension and flexion at 1.05 rad/s were determined twice at an interval of 6 months in 24 male soccer players aged 12-13 years and 11 age- and body height-matched non-athletes. After 6 months, muscle CSA and dynamic strength increased without significant interaction of time and group. Thigh total muscle CSA was not significantly affected by group, but the value relative to either thigh CSA or body mass was higher in soccer players. While knee flexion strength was similar between the 2 groups, knee extension strength was greater in soccer players than in non-athletes, even in terms of strength relative to CSA. The current results indicate that, compared with age- and body height-matched non-athletes, early adolescent soccer players are characterized by higher relative distribution of muscle mass within the thigh and higher knee extension strength relative to the quadriceps CSA. During the growth stage in which body height begins to increase markedly, however, participation in competitive soccer training does not increase the rate of development in thigh muscularity and strength.

Oxidative stress contributes to muscular fatigue. GSH is the major intracellular antioxidant, the biosynthesis of which is dependent on cysteine availability. We hypothesized that supplementation with a whey-based cysteine donor [Immunocal (HMS90)] designed to augment intracellular GSH would enhance performance. Twenty healthy young adults (10 men, 10 women) were studied presupplementation and 3 mo postsupplementation with either Immunocal (20 g/day) or casein placebo. Muscular performance was assessed by whole leg isokinetic cycle testing, measuring peak power and 30-s work capacity. Lymphocyte GSH was used as a marker of tissue GSH. There were no baseline differences (age, ht, wt, %ideal wt, peak power, 30-s work capacity). Follow-up data on 18 subjects (9 Immunocal, 9 placebo) were analyzed. Both peak power [13 +/- 3.5 (SE) %, P < 0.02] and 30-s work capacity (13 +/- 3.7%, P < 0.03) increased significantly in the Immunocal group, with no change (2 +/- 9.0 and 1 +/- 9.3%) in the placebo group. Lymphocyte GSH also increased significantly in the Immunocal group (35.5 +/- 11.04%, P < 0.02), with no change in the placebo group (-0.9 +/- 9.6%). This is the first study to demonstrate that prolonged supplementation with a product designed to augment antioxidant defenses resulted in improved volitional performance.

Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus.

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers of muscular dystrophy have long been desired. MicroRNAs (miRNAs) are small, ∼22 nucleotide, noncoding RNAs which play important roles in the regulation of gene expression at the post-transcriptional level. Recently, it has been reported that miRNAs exist in blood. In this study, we hypothesized that the expression levels of specific serum circulating miRNAs may be useful to monitor the pathological progression of muscular diseases, and therefore explored the possibility of these miRNAs as new biomarkers for muscular diseases. To confirm this hypothesis, we quantified the expression levels of miRNAs in serum of the dystrophin-deficient muscular dystrophy mouse model, mdx, and the canine X-linked muscular dystrophy in Japan dog model (CXMD(J)), by real-time PCR. We found that the serum levels of several muscle-specific miRNAs (miR-1, miR-133a and miR-206) are increased in both mdx and CXMD(J). Interestingly, unlike CK levels, expression levels of these miRNAs in mdx serum are little influenced by exercise using treadmill. These results suggest that serum miRNAs are useful and reliable biomarkers for muscular dystrophy.

The drive for muscularity and associated behaviors (e.g., exercising and dieting) are of growing importance for men in Western societies. In its extreme form, it can lead to body image concerns and harmful behaviors like over-exercising and the misuse of performance-enhancing substances. Therefore, investigating factors associated with the drive for muscularity, especially in vulnerable populations like bodybuilders and weight trainers can help identify potential risk and protective factors for body image problems. Using a biopsychosocial framework, the aim of the current study was to explore different factors associated with drive for muscularity in weight-training men. To this purpose, German-speaking male weight trainers (N = 248) completed an online survey to determine the extent to which biological, psychological, and sociocultural factors contribute to drive for muscularity and its related attitudes and behaviors. Using multiple regression models, findings showed that media ideal body internalization was the strongest positive predictor for drive for muscularity, while age (M = 25.9, SD = 7.4) held the strongest negative association with drive for muscularity. Dissatisfaction with muscularity, but not with body fat, was related to drive for muscularity. The fat-free mass index, a quantification of the actual degree of muscularity of a person, significantly predicted drive for muscularity-related behavior but not attitudes. Body-related aspects of self-esteem, but not global self-esteem, were significant negative predictors of drive for muscularity. Since internalization of media body ideals presented the highest predictive value for drive for muscularity, these findings suggest that media body ideal internalizations may be a risk factor for body image concerns in men, leading, in its most extreme form to disordered eating or muscle dysmorphia. Future research should investigate the relations between drive for muscularity, age, body composition

The drive for muscularity and associated behaviors (e.g., exercising and dieting) are of growing importance for men in Western societies. In its extreme form, it can lead to body image concerns and harmful behaviors like over-exercising and the misuse of performance-enhancing substances. Therefore, investigating factors associated with the drive for muscularity, especially in vulnerable populations like bodybuilders and weight trainers can help identify potential risk and protective factors for body image problems. Using a biopsychosocial framework, the aim of the current study was to explore different factors associated with drive for muscularity in weight-training men. To this purpose, German-speaking male weight trainers (N = 248) completed an online survey to determine the extent to which biological, psychological, and sociocultural factors contribute to drive for muscularity and its related attitudes and behaviors. Using multiple regression models, findings showed that media ideal body internalization was the strongest positive predictor for drive for muscularity, while age (M = 25.9, SD = 7.4) held the strongest negative association with drive for muscularity. Dissatisfaction with muscularity, but not with body fat, was related to drive for muscularity. The fat-free mass index, a quantification of the actual degree of muscularity of a person, significantly predicted drive for muscularity-related behavior but not attitudes. Body-related aspects of self-esteem, but not global self-esteem, were significant negative predictors of drive for muscularity. Since internalization of media body ideals presented the highest predictive value for drive for muscularity, these findings suggest that media body ideal internalizations may be a risk factor for body image concerns in men, leading, in its most extreme form to disordered eating or muscle dysmorphia. Future research should investigate the relations between drive for muscularity, age, body composition

Weakness resulting from spinal muscular atrophy causes severe limitations in functional mobility. The early introduction of power mobility has potential to enhance development and mitigate disability. These outcomes are achieved by simulating normal skill acquisition and by promoting motor learning, visuospatial system development, self-exploration, cognition, and social development. There are few reports on early power mobility in spinal muscular atrophy, and it is typically not prescribed until school age. The authors evaluated 6 children under age 2 years with neuromuscular disease (5 spinal muscular atrophy, 1 congenital muscular dystrophy) for power mobility. Parents recorded the practice hours necessary to achieve independence using the Power Mobility Skills Checklist. Four children achieved independence in all items on the checklist by 7.9 months (range: 73-458 days). Introduction of early power mobility is feasible in spinal muscular atrophy patients under age 2 years and should be introduced in late infancy when children typically acquire locomotor skills.

This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black males used steroids less frequently and delayed initiation compared to white males. Compared to males without a Duchenne muscular dystrophy family history, males with known family history were half as likely to use steroids. Duration of steroid use increased over time and age at initiation decreased. Racial/ethnic disparities exist for steroid use and should be addressed to improve outcome and quality of life for boys with Duchenne muscular dystrophy.

To investigate the effects of both an active warm-up (AWU) and the diurnal increase in body temperature on muscular power. Eight male subjects performed maximal cycling sprints in the morning (7:00-9:00 a.m.) and afternoon (5:00-7:00 p.m.) either after an AWU or in a control condition. The AWU consisted of 12 min of pedaling at 50% of & OV0312;O2 max inter-spersed with three brief accelerations of 5 s. Rectal temperature, maximal force developed during the cycling sprint, and muscular power were higher in the afternoon than in the morning (P<0.05). Rectal temperature, calculated muscular temperature, and muscular power were higher after AWU than in control condition (P<0.05). The beneficial effect of an AWU can be combined with that of the diurnal increase in central temperature to improve muscular power.

The goal of this study was to examine whether the drive for thinness and the drive for muscularity occur concurrently among late adolescents and to understand the body attitudes associated with desiring a thinner and/or a more muscular physique. Participants included 235 college freshmen who participated in a larger study of body image and eating attitudes. The majority of individuals reported having both a high drive for thinness and a high drive for muscularity (65.4%). Additionally, the presence of both drives significantly predicted body compulsivity and body anxiety among females, and body-esteem among males. Results of the current study provide considerable evidence that a drive for thinness and a drive for muscularity are not mutually exclusive. Furthermore, the degree to which an individual strives for thinness and/or muscularity has differential effects on their body attitudes.

The development of a drive for muscularity among boys has been linked to various cultural influences, one of which is exposure to mass media depicting the muscular male body ideal. We sought to determine whether self-reported exposure to four ideal-body magazine genres (health/fitness, fashion, sports, and gaming) predicted an increased drive for muscularity 1 year later. A sample of 104 Black and 77 White preadolescent boys (mean age 8.77) participated in a 2-wave longitudinal panel study. Controlling Wave 1 grade, perceived thinness/adiposity, and drive for muscularity, exposure to video gaming magazines predicted a significant increase in Wave 2 drive for muscularity, but only for White boys. Discussion calls for the inclusion of video gaming magazine exposure measures in future research on print media and male body ideals, along with empirical exploration of racial themes in gaming magazines.

Objective To assess the impact of muscular strength on mortality in men with hypertension. Background Muscular strength is inversely associated with mortality in healthy men, but this association has not been examined in men with hypertension. Methods We followed 1506 hypertensive men aged ≥ 40 years enrolled in the Aerobics Center Longitudinal Study from 1980 to 2003. Participants received an extensive medical examination at baseline. Muscular strength was quantified by combining one repetition maximum (1-RM) measures for leg and bench press, and cardiorespiratory fitness (CRF) assessed by maximum exercise test on a treadmill. Results During an average follow-up of 18.3 years, 183 deaths occurred. Age adjusted death rates per 10 000 man-years across incremental thirds of muscular strength were 81.8, 65.5 and 52.0 (P<0.05 for linear trend). Multivariable Cox regression hazard ratios were 1.0 (reference), 0.81 (95% confidence interval, 0.57 to 1.14), and 0.59 (0.40 to 0.86) across incremental thirds of muscular strength. After further adjustment for CRF, those participants in the upper third of muscular strength still had a lower risk of death (0.66; 0.45 to 0.98). In the muscular strength and CRF combined analysis, men simultaneously in the upper third of muscular strength and high fitness group had the lowest mortality risk among all combination groups (0.49; 0.30 to 0.82), with men in the lower third of muscular strength and low fitness group as reference. Conclusions High levels of muscular strength appear to protect hypertensive men against all-cause mortality, and this is in addition to the benefit provided by CRF. PMID:21527158

A number of muscular dystrophies are associated with the defective glycosylation of [alpha]-dystroglycan and many are now known to result from mutations in a number of genes encoding putative or known glycosyltransferases. These diseases include severe forms of congenital muscular dystrophy (CMD) such as Fukuyama type congenital muscular dystrophy…

A number of muscular dystrophies are associated with the defective glycosylation of [alpha]-dystroglycan and many are now known to result from mutations in a number of genes encoding putative or known glycosyltransferases. These diseases include severe forms of congenital muscular dystrophy (CMD) such as Fukuyama type congenital muscular dystrophy…

OBJECTIVE: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. METHODS: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. RESULTS: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. CONCLUSIONS: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis. PMID:25410841

Patients with Duchenne muscular dystrophy (DMD) or spinal muscular atrophy (SMA), both neuromuscular diseases, sustain spinal scoliosis in the course of their disease. To reduce the concomitant major morbidity and to improve their quality of life, patients require surgical spine stabilization. This can lead to complications like respiratory, cardiac or neurological complications or wound healing disorders (WHD). To find out the different complexities and risk factors increasing the chance to develop a WHD, the inpatient database was analyzed. We performed a retrospective statistical study. Therefore, we analyzed the inpatient database of 180 patients (142 DMD and 38 SMA patients). The focus was on WHD. To figure out the risk factors leading to WHD, we conducted a logistic regression. Cardiac complications occurred most frequently, followed by pulmonary complications and neurological lesions. Fifty-seven out of 180 patients developed a WHD. In 23 cases the WHD was aseptic, in the other 34 cases dermal organisms, Pseudomonas species and intestinal organisms were responsible. By means of the logistic regression, we were able to identify two more risk factors, in addition to diagnosis and gender, for developing a WHD in our patients: the year of surgery and the direction of pelvic tilt. Most common complications following scoliosis surgery are respiratory and cardiac complications. WHD is a severe complication that implies a prolonged therapy. Some risk factors for developing WHD could be identified in this analysis. Specifically, these were the date of surgery and the direction of pelvic tilt.

In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

Background In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. Methods We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ months) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. Results We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. Conclusion These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively. PMID:26672735

Patients with advanced muscular dystrophy frequently develop ventilatory failure. Currently respiratory impairment usually is assessed by measuring vital capacity and the mouth pressure generated during a maximal inspiratory maneuver (PI,max), neither of which directly measures ventilatory capacity. We assessed inspiratory flow reserve in 26 boys [mean (SD) age 12.8 (3.8) years] with Duchenne muscular dystrophy (DMD) without ventilatory failure and in 28 normal boys [mean (SD) age 12.6 (1.9) years] by analyzing the ratio between the largest inspiratory flow during tidal breathing (V'I,max(t)) and during a forced vital capacity maneuver (V'I,max(FVC), (V'I,max(t)/V'I,maxFVC). We have compared this ratio with the forced vital capacity FVC and PI,max measured at functional residual capacity. Mean PI,max was -90(30)cmH2O, average 112% (range 57-179%) of predicted values in control boys and -31(11)cmH2O, average 40% predicted values in DMD boys (control vs DMD, P < 0.001). FVC was reduced in DMD boys [59(20)% predicted values vs 86(10)% predicted values in controls, P < 0.01]. Absolute V'I,max(FVC) was strongly related to FVC in both control and DMD boys; V'I,max(FVC) (expressed as FVC. s(-1)) was not related to PI,max in either group. The mean V'I,max(t)/V'I,max(FVC); ratio was higher in DMD 0.22 (0.08) than in controls 0.12 (0.03) (P < 0.001) indicating a reduction in inspiratory flow reserve in DMD. Inspiratory flow reserve was within the normal range in 8 of 19 DMD patients with PI,max less than 50% of predicted values. We conclude that measurement of inspiratory flow reserve (V'I,max(t)/V'I,maxFVC ratio) provides a simple and direct assessment of dynamic inspiratory muscle function which is not replicated by static measurement of PI,max or vital capacity and might be useful in assessment of respiratory impairment in boys with Duchenne muscular dystrophy. Follow-up studies are required to establish whether measures of inspiratory flow reserve are of clinical value

A 69-year-old woman presented a dropped head, caused by severe neck extensor weakness that had started two years before. She had also developed a mild degree of dysphagia, rhinolalia, eyelid ptosis and proximal limb weakness during the last months. EMG revealed myopathic changes. Muscle MRI detected fatty infiltration in the posterior neck muscles and tongue. Muscle biopsy revealed fiber size variations, sporadic rimmed vacuoles, small scattered angulated fibers and a patchy myofibrillar network. Genetic analysis revealed homozygous (GCN)11 expansions in the PABPN1 gene that were consistent with recessive oculopharyngeal muscular dystrophy (OPMD). There are a few reports of the recessive form, which has a later disease onset with milder symptoms and higher clinical variability than the typical dominantly inherited form. This patient, who is the first Italian and the eighth worldwide reported case of recessive OPMD, is also the first case of OPMD with dropped-head syndrome, which thus expands the clinical phenotype of recessive OPMD.

SUMMARY Dystroglycan, which serves as a major extracellular matrix receptor in muscle and the central nervous system, requires extensive O-glycosylation to function. We identified a dystroglycan missense mutation (Thr192→Met) in a woman with limb-girdle muscular dystrophy and cognitive impairment. A mouse model harboring this mutation recapitulates the immunohistochemical and neuromuscular abnormalities observed in the patient. In vitro and in vivo studies showed that the mutation impairs the receptor function of dystroglycan in skeletal muscle and brain by inhibiting the post-translational modification, mediated by the glycosyltransferase LARGE, of the phosphorylated O-mannosyl glycans on α-dystroglycan that is required for high-affinity binding to laminin. PMID:21388311

Impaired muscular microcirculation in lower extremities is common in many peripheral vascular diseases (PVD), especially the peripheral arterial disease (PAD). There is a need for an imaging method that can be used to noninvasively visualize depth-resolved microcirculation within muscle tissues. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ~2 mm, with an imaging sensitivity to the blood flow at ~160 μm/s. In this paper, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at microcirculatory level resolution, within skeletal muscles in mice. By use of the mouse model of hind-limb ischemia, we show OMAG can assess the perfusion changes caused by ligation. These findings indicate that OMAG is a promising technique to effectively study skeletal muscle-related vascular disease and their pharmacologic therapies.

Spinal muscular atrophy is the second most frequent autosomal-recessive disorder in Europeans. There are no published epidemiological data on SMA in Estonia and other Baltic countries. The aim of this study was to estimate the incidence of SMA I in Estonia. All patients with SMA I diagnosed between January 1994 and December 2003 were included in the study. The diagnosis was established on the basis of neurological evaluation, ENMG findings, molecular studies and muscle biopsy. PCR and restriction enzyme analysis was used to detect the homozygous deletion of the SMN1 gene. A total of 9 cases of SMA I were identified during this 10-year period. The incidence of SMA I in Estonia is 1 in 14,400 live births, which is similar to the result from Hungary but lower than average incidence in the world. Only one of the patients was female. Typical SMN1 gene deletion was found in all cases.

Laminins are extracellular matrix (ECM) proteins that play an important role in cellular function and tissue morphogenesis. In the peripheral nervous system (PNS), laminins are expressed in Schwann cells and participate in their development. Mutations in laminin subunits expressed in the PNS and in skeleton muscle may cause peripheral neuropathies and muscular dystrophy in both humans and mice. Recent studies using gene knockout technology, such as cell-type specific gene targeting techniques, revealed that laminins and their receptors mediate Schwann cell and axon interactions. Schwann cells with disrupted laminin expression exhibit impaired proliferation and differentiation and also undergo apoptosis. In this review, we focus on the potential molecular mechanisms by which laminins participate in the development of Schwann cells.

Duchenne muscular dystrophy (DMD) is a genetic, lethal, muscle disorder caused by the loss of the muscle protein, dystrophin, leading to progressive loss of muscle fibers and muscle weakness. Drug discovery efforts targeting DMD have used two main approaches: (1) the restoration of dystrophin expression or the expression of a compensatory protein, and (2) the mitigation of downstream pathological mechanisms, including dysregulated calcium homeostasis, oxidative stress, inflammation, fibrosis, and muscle ischemia. The aim of this review is to introduce the disease, its pathophysiology, and the available research tools to a drug discovery audience. This review will also detail the most promising therapies that are currently being tested in clinical trials or in advanced preclinical models.

Duchenne muscular dystrophy (DMD) is a severe genetic disorder caused by loss of function of the dystrophin gene on the X chromosome. Gene augmentation of dystrophin is challenging due to the large size of the dystrophin cDNA. Emerging genome editing technologies, such as TALEN and CRISPR-Cas9 systems, open a new erain the restoration of functional dystrophin and are a hallmark of bona fide gene therapy. In this review, we summarize current genome editing approaches, properties of target cell types for ex vivo gene therapy, and perspectives of in vivo gene therapy including genome editing in human zygotes. Although technical challenges, such as efficacy, accuracy, and delivery of the genome editing components, remain to be further improved, yet genome editing technologies offer a new avenue for the gene therapy of DMD.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a hereditary motor neuron disease that affects males, caused by the expansion of a polyglutamine (polyQ) tract in androgen receptor (AR). Female carriers are usually asymptomatic. The transgenic mouse (Tg) model carrying a full-length human AR with expanded polyQ has significant gender-related motor impairment. This phenotype is inhibited by castration, which prevents nuclear translocation of mutant AR. Leuprorelin, an LHRH agonist that reduces testosterone release from the testis, also rescues motor dysfunction and nuclear accumulation of mutant AR in the male Tg. Over-expression of a molecular chaperone HSP70, which renatures misfolded mutant AR, ameliorates neuromuscular phenotypes of the Tg by reducing nuclear-localized mutant AR. HSP70 appears to enhance the degradation of mutant AR via ubiquitin-proteasome pathway. These experimental approaches indicate the possibility of clinical application of drugs, such as leuprorelin, for SBMA patients.

We tested the ability of eight Parkinson's disease (PD) patients with clearly asymmetrical right-sided motor signs and eight control subjects to assess different levels of muscular forces. In Experiment 1, subjects had first to produce a target-force with one hand (the reference hand) with the assistance of visual feedback, and then match that force with the other hand (the matching hand) without any visual feedback. In Experiment 2, they had to produce a target-force with one hand and then estimate it by attributing a numerical value. In Experiment 1, the results showed that PD patients could normally reach the target-forces with the more affected left hand but they were impaired in inter-manual force transfer. They were also impaired, in Experiment 2, in estimating forces produced by their more affected hand. Our findings suggest that PD patients present a deficit in sensing motor effort. Effort awareness might be mediated by the basal ganglia.

Introduction Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. PMID:23836324

Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterised by the selective loss of particular groups of motor neurones in the anterior horn of the spinal cord with concomitant muscle weakness. To date, no effective treatment is available, however, there are ongoing clinical trials are in place which promise much for the future. However, there remains an ongoing problem in trying to link a single gene loss to motor neurone degeneration. Fortunately, given successful disease models that have been established and intensive studies on SMN functions in the past ten years, we are fast approaching the stage of identifying the underlying mechanisms of SMA pathogenesis Here we discuss potential disease modifying factors on motor neurone vulnerability, in the belief that these factors give insight into the pathological mechanisms of SMA and therefore possible therapeutic targets.

Statins have demonstrated substantial benefits in supporting cardiovascular health. Older individuals are more likely to experience the well-known muscle-related side effects of statins compared with younger individuals. Elderly females may be especially vulnerable to statin-related muscle disorder. This review will collate and discuss statin-related muscular effects, examine their molecular and genetic basis, and how these apply specifically to elderly women. Developing strategies to reduce the incidence of statin-induced myopathy in older adult women could contribute to a significant reduction in the overall incidence of statin-induced muscle disorder in this vulnerable group of patients. Reducing statin-related muscle disorder would likely improve overall patient compliance, thereby leading to an increase in improved short- and long-term outcomes associated with appropriate use of statins. PMID:23355775

Congenital muscular dystrophy type 1A (MDC1A) is an autosomal recessive disorder characterized by hypotonia, elevated serum creatine kinase level, delayed motor milestones, white matter changes observed by brain magnetic resonance imaging, and normal intelligence. A mutation in the laminin α2 (LAMA2) gene, located at 6q22-23, is a genetic cause of MDC1A. Patients have merosin (laminin α2)-deficient skeletal muscles. However, the degree of merosin expression ranges from total absence to partial reduction. Patients with residual merosin expression have more variable and milder phenotypes than those with absolute merosin deficiency. We observed a Korean girl with MDC1A with residual merosin expression. Clinical presentation of this patient was typical except for late onset of the disease and external capsule involvement. Immunohistochemical staining of muscle fibers including merosin, is important to evaluate patients with hypotonia, delayed motor development, and abnormal white matter changes.

Muscle strength can define the general muscular fitness (MF) measurable through hand-grip strength (HG), which is a factor that relates to the health of people of different ages. In this study we evaluated the muscle strength together with a bioimpedance electric analysis in 223 healthy Colombian adult subjects. The bioelectrical impedance vector analysis (BIVA) was conducted to determine the resistance (R), reactance (Xc) and phase angle (PhA). We classified the subjects into three groups (for tertiles), obtaining lower values of R and Xc in subjects with lower HG, plus a high correlation between PhA and HG. An increase in the level of PhA is associated with a high level of MF in a sample of healthy Latin American adult men. The BIVA’s parameters and PhA are a potentially effective preventive measure to be integrated into routine screening in the clinical setting. PMID:27384579

An explicit finite element scheme is developed for biological muscular hydrostats such as squid tentacles, octopus arms and elephant trunks. The scheme is implemented by embedding muscle fibers in finite elements. In any given element, the fiber orientation can be assigned arbitrarily and multiple muscle directions can be simulated. The mechanical stress in each muscle fiber is the sum of active and passive parts. The active stress is taken to be a function of activation state, muscle fiber shortening velocity and fiber strain; while the passive stress depends only on the strain. This scheme is tested by simulating extension of a squid tentacle during prey capture; our numerical predictions are in close correspondence with existing experimental results. It is shown that the present finite element scheme can successfully simulate more complex behaviors such as torsion of a squid tentacle and the bending behavior of octopus arms or elephant trunks.

Two DNA markers, a random DNA fragment 754 and the cDNA sequence encoding the gene for ornithine transcarbamylase (OTC) have been studied in kindreds segregating for Duchenne muscular dystrophy. 754 and OTC are located close physically to the mutation in the region Xp21 below the breakpoints in two Duchenne females. The genetic distance was found to be approximately 10cM between 754 and DMD (two crossovers in 26 meioses) and to be approximately 10cM between OTC and DMD (two crossovers in 26 meioses). Physical data suggest the order DMD-754-OTC. The frequency of recombination compared to physical distance between these markers and DMD suggests that there may be a hot spot of recombination. The relevance of these observations for the isolation of the DMD mutation and clinical use of these probes is discussed. Images PMID:3859837

During contraction and stretching, muscles change shape and size, and produce a deformation of skin tissues and a modification of the body segment shape. In human motion analysis, it is very important to take into account these phenomena. The aim of this work is the evaluation of skin and muscular deformation, and the modeling of body segment elastic behavior obtained by analysing video sequences that capture a muscle contraction. The soft tissue modeling is accomplished by using triangular meshes that automatically adapt to the body segment during the execution of a static muscle contraction. The adaptive triangular mesh is built on reference points whose motion is estimated by using non linear operators. Experimental results, obtained by applying the proposed method to several video sequences, where biceps brachial isometric contraction was present, show the effectiveness of this technique.

In order to better understand the complexity of congenital muscular dystrophies (CMD) and develop new strategies to cure them, it is important to establish new disease models. Due to its numerous helpful attributes, the zebrafish has recently become a very powerful animal model for the study of CMD. For some CMD, this vertebrate model is phenotypically closer to human pathology than the murine model. Over the last few years, researchers have developed innovative techniques to screen rapidly and on a large scale for muscle defects in zebrafish. Furthermore, new genome editing techniques in zebrafish make possible the identification of new disease models. In this review, the major attributes of zebrafish for CMD studies are discussed and the principal models of CMD in zebrafish are highlighted.

Highly anticipated as new disease-modifying treatments for Duchenne muscular dystrophy (DMD), therapeutics by BioMarin Pharmaceutical (Kyndrisa™; drisapersen) and Sarepta Therapeutics (eteplirsen; AVI-4658) both recently received negative FDA reviews and are now facing battles for approval in the U.S. At present, BioMarin is committed to working with the FDA to forge a pathway to approval following the failure of its NDA, while Sarepta awaits the formal decision on its NDA, which is expected by late May 2016. Despite the critical nature of both reviews, analysts consider that there is still a narrow possibility of approval of both drugs. According to Consensus forecasts from Thomson Reuters Cortellis for Competitive Intelligence, Kyndrisa is forecast to achieve sales of USD 533.71 million in 2021.

To explore the genotypic and clinical features and laboratory examinations of spinal muscular atrophy type 3 (SMA III). Results of genetic testing and laboratory exams of 18 SMA III patients were collected and analyzed. The average age of onset of patients was 6.1 years, with the course of disease lasting from 13 months to 28 years. All patients became symptomatic with lower extremity muscle weakness. The symptoms gradually aggregated, with proximal lower limb muscle becoming atrophic and proximal upper limb muscle becoming weak. Genetic testing indicated that all subjects possessed homozygous deletions of SMN1 gene. Electromyography (EMG) of 15 subjects indicated neurogenic damage. Whilst younger patients had normal level of creatine kinase (CK), elder patients had higher level of CK, though no linear correlation was found. Full understanding of Clinical, especially the growth features of SMA III, in combination with genetic testing, can facilitate diagnosis and early intervention of the disease.

Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease that results in progressive dysfunction of motor neurons of the anterior horn of the spinal cord. SMA is caused by the loss of full-length protein expression from the survival of motor neuron 1 (SMN1) gene. The disease has a unique genetic profile as it is autosomal recessive for the loss of SMN1, but a nearly identical homolog, SMN2, acts as a disease modifier whose expression is inversely correlated to clinical severity. Targeted therapeutic approaches primarily focus on increasing the levels of full-length SMN protein, through either gene replacement or regulation of SMN2 expression. There is currently no US FDA approved treatment for SMA. This is an exciting time as multiple efforts from academic and industrial laboratories are reaching the preclinical and clinical testing stages.

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. The disease originates from low levels of SMN protein due to deletion and/or mutations of SMN1 coupled with the inability of SMN2 to compensate for the loss of SMN1. While SMN1 and SMN2 are nearly identical, SMN2 predominantly generates a truncated protein (SMNΔ7) due to skipping of exon 7, the last coding exon. Several avenues for SMA therapy are being explored, including means to enhance SMN2 transcription, correct SMN2 exon 7 splicing, stabilize SMN/SMNΔ7 protein, manipulate SMN-regulated pathways and SMN1 gene delivery by viral vectors. This review focuses on the aspects of target discovery, validations and outcome measures for a promising therapy of SMA. PMID:25068989

The authors report 4 cases of inter and intra-muscular lipoma of the shoulder and make a review of the diagnosis of this localization. All 4 cases had shoulder pain and some limitation of shoulder motion, one had hypoesthesia on the lateral side of the arm. 3 had magnetic resonance imaging (MRI) and two ultrasonography examination, three of them had a surgical resection and for one surgery was considered too aggressive and had a MRI control one year later. There was no problem for the surgical procedure and the histology confirmed the diagnosis. The last patient had a rehabilitation program and the MRI control showed lesion stability. Lipoma are rare, X-rays, ultra-sonography and CT scans are not sufficient, MRI is the best exploration to differentiate lipoma and lipo-sarcoma, but the main problem is for low grade sarcoma. Histology is the only way to make the diagnosis with the whole tumor.

The purpose of this study was to assess the relationships between obesity and measures of back and core muscular endurance in firefighters. Methods. A cross-sectional study was conducted in career firefighters without low back pain. Obesity measures included body mass index (BMI) and body fat percentage assessed with air displacement plethysmography. Muscular endurance was assessed with the Modified Biering Sorensen (back) and Plank (core) tests. Relationships were explored using t-tests and regression analyses. Results. Of the 83 participants enrolled, 24 (29%) were obese (BMI ≥ 30). Back and core muscular endurance was 27% lower for obese participants. Significant negative correlations were observed for BMI and body fat percentage with back and core endurance (r = −0.42 to −0.52). Stepwise regression models including one obesity measure (BMI, body fat percentage, and fat mass/fat-free mass), along with age and self-reported physical exercise, accounted for 17–19% of the variance in back muscular endurance and 29–37% of the variance in core muscular endurance. Conclusions. Obesity is associated with reduced back and core muscular endurance in firefighters, which may increase the risk of musculoskeletal injuries. Obesity should be considered along with back and core muscular endurance when designing exercise programs for back pain prevention in firefighters. PMID:23213491

The aim of this cross-sectional study was to examine the influence of muscular strength on carotid intima-media thickness (cIMT) in children, controlling for the effect of cardiorespiratory fitness (CRF) and central adiposity and to examine if differences among muscular strength tertiles translate to physiological differences. We assessed cIMT of the common carotid artery in 366 children between 11-12 years of age (191 girls). Measures included cIMT assessed with high-resolution ultrasonography, a maximal handgrip strength test, body fat mass and lean mass from DXA and CRF determined using a maximal cycle ergometer test. Association between muscular strength and cIMT adjusted for CRF and central adiposity, as measured by trunk fat, was tested with multiple linear regression analysis. Differences in risk factors among muscular strength groups were tested with ANOVA. The Muscular Strength Index (MSI) was inversely associated with cIMT independently of CRF and central adiposity (p<0.05). The low MSI group had the highest values of cIMT, waist circumference and systolic blood pressure and the lowest CRF (p<0.05). There was an inverse and independent association between muscular strength and cIMT. Low muscular strength was associated with higher levels of cardiovascular disease risk factors in children.

The purpose of this study was to assess the relationships between obesity and measures of back and core muscular endurance in firefighters. Methods. A cross-sectional study was conducted in career firefighters without low back pain. Obesity measures included body mass index (BMI) and body fat percentage assessed with air displacement plethysmography. Muscular endurance was assessed with the Modified Biering Sorensen (back) and Plank (core) tests. Relationships were explored using t-tests and regression analyses. Results. Of the 83 participants enrolled, 24 (29%) were obese (BMI ≥ 30). Back and core muscular endurance was 27% lower for obese participants. Significant negative correlations were observed for BMI and body fat percentage with back and core endurance (r = -0.42 to -0.52). Stepwise regression models including one obesity measure (BMI, body fat percentage, and fat mass/fat-free mass), along with age and self-reported physical exercise, accounted for 17-19% of the variance in back muscular endurance and 29-37% of the variance in core muscular endurance. Conclusions. Obesity is associated with reduced back and core muscular endurance in firefighters, which may increase the risk of musculoskeletal injuries. Obesity should be considered along with back and core muscular endurance when designing exercise programs for back pain prevention in firefighters.

Low back pain is a leading cause of disability in firefighters and is related to poor muscular endurance. This study examined the impact of supervised worksite exercise on back and core muscular endurance in firefighters. A cluster randomized controlled trial was used for this study. The study occurred in fire stations of a municipal fire department (Tampa, Florida). Subjects were 96 full-duty career firefighters who were randomly assigned by fire station to exercise (n = 54) or control (n = 42) groups. Exercise group participants completed a supervised exercise targeting the back and core muscles while on duty, two times per week for 24 weeks, in addition to their usual fitness regimen. Control group participants continued their usual fitness regimen. Back and core muscular endurance was assessed with the Biering-Sorensen test and plank test, respectively. Changes in back and core muscular endurance from baseline to 24 weeks were compared between groups using analysis of covariance and linear mixed effects models. After 24 weeks, the exercise group had 12% greater (p = .021) back muscular endurance and 21% greater (p = .0006) core muscular endurance than did the control group. The exercise intervention did not disrupt operations or job performance. A supervised worksite exercise program was safe and effective in improving back and core muscular endurance in firefighters, which could protect against future low back pain.

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

Summary Background: it is well established that muscle strength is a determinant factor in judo. However, little data are available for African athletes. Therefore, the aim of this study was to provide reference data of the muscular strength profile (MSP) for an African team, Tunisian judo team. Methods: the study was conducted among ten international judo athletes from Tunisia. To determine their MSP, we used an isokinetic dynamometer to assess Hamstrings, Quadriceps of both knees and external, internal rotators of both shoulders. The angular velocities of the assessments were; 90, 180, 240°/s for the knees and 60, 120°/s for the shoulders. Results: MSP was determined based on two parameters; the maximum peak torque (PT) of each muscle and the ratio agonistic/antagonistic muscles (R). The knee extensors and flexors in the “supporting leg” had higher PT than in the “attacking leg”; respectively, 245N.m versus 237 (p<0.05) and 147 N.m versus 145 (p>0.05). R was normal for both legs. Furthermore, both rotators of the dominant shoulder had higher PT; 84 N.m versus 71 for the internal rotators (p<0.05) and 34,7 N.m versus 29,0 for the lateral rotators (p<0.05). Inversely, R was higher in the non-dominant side; 45% versus 35, p<0.05). Conclusion: the MSP of the selected elites Tunisian judo athletes was characterized by 3 major features; a strength of the quadriceps in the standing leg significantly higher than in the attacking leg, a normal muscular balance Hamstrings/quadriceps in both legs and a strength of the shoulder’ rotators higher in the dominant side. PMID:25332926

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying

Abstract The principal function of the lymphatic system is to transport lymph from the interstitium to the nodes and then from the nodes to the blood. In doing so lymphatics play important roles in fluid homeostasis, macromolecular/antigen transport and immune cell trafficking. To better understand the genes that contribute to their unique physiology, we compared the transcriptional profile of muscular lymphatics (prenodal mesenteric microlymphatics and large, postnodal thoracic duct) to axillary and mesenteric arteries and veins isolated from rats. Clustering of the differentially expressed genes demonstrated that the lymph versus blood vessel differences were more profound than between blood vessels, particularly the microvessels. Gene ontology functional category analysis indicated that microlymphatics were enriched in antigen processing/presentation, IgE receptor signaling, catabolic processes, translation and ribosome; while they were diminished in oxygen transport, regulation of cell proliferation, glycolysis and inhibition of adenylate cyclase activity by G-proteins. We evaluated the differentially expressed microarray genes/products by qPCR and/or immunofluorescence. Immunofluorescence documented that multiple MHC class II antigen presentation proteins were highly expressed by an antigen-presenting cell (APC) type found resident within the lymphatic wall. These APCs also expressed CD86, a co-stimulatory protein necessary for T-cell activation. We evaluated the distribution and phenotype of APCs within the pre and postnodal lymphatic network. This study documents a novel population of APCs resident within the walls of muscular, prenodal lymphatics that indicates novel roles in antigen sampling and immune responses. In conclusion, these prenodal lymphatics exhibit a unique profile that distinguishes them from blood vessels and highlights the role of the lymphatic system as an immunovascular system linking the parenchymal interstitium, lymph nodes and the

The cardiofaciocutaneous (CFC) syndrome is characterized by congenital heart defect, developmental delay, peculiar facial appearance with bitemporal constriction, prominent forehead, downslanting palpebral fissures, curly sparse hair and abnormalities of the skin. CFC syndrome phenotypically overlaps with Noonan and Costello syndromes. Mutations of several genes (PTPN11, HRAS, KRAS, BRAF, MEK1 and MEK2), involved in the mitogen-activated protein kinase (MAPK) pathway, have been identified in CFC-Costello-Noonan patients. Coenzyme Q10 (CoQ10), a lipophilic molecule present in all cell membranes, functions as an electron carrier in the mitochondrial respiratory chain, where it transports electrons from complexes I and II to complex III. CoQ10 deficiency is a rare treatable mitochondrial disorder with various neurological (cerebellar ataxia, myopathy, epilepsy, mental retardation) and extraneurological (cardiomyopathy, nephropathy) signs that are responsive to CoQ10 supplementation. We report the case of a 4-year-old girl who presented a CFC syndrome, confirmed by the presence of a pathogenic R257Q BRAF gene mutation, together with a muscular CoQ10 deficiency. Her psychomotor development was severely impaired, hindered by muscular hypotonia and ataxia, both improving remarkably after CoQ10 treatment. This case suggests that there is a functional connection between the MAPK pathway and the mitochondria. This could be through the phosphorylation of a nuclear receptor essential for CoQ10 biosynthesis. Another hypothesis is that K-Ras, one of the proteins composing the MAPK pathway, might be recruited into the mitochondria to promote apoptosis. This case highlights that CoQ10 might contribute to the pathogenesis of CFC syndrome.

We hypothesized that resistance training with combined eccentric and concentric actions, and concentric action only, should yield similar changes in muscular strength. Subjects in a free weight group trained three times a week for 12 wk with eccentric and concentric actions (FW, n = 16), a second group trained with concentric-only contractions using hydraulic resistance (HY; n = 12), and a control group did not train (n = 11). Training for FW and HY included five sets of supine bench press and upright squat at an intensity of 1-6 repetition maximum (RM) plus five supplementary exercises at 5-10 RM for a total of 20 sets per session for approximately 50 min. Testing at pre-, mid-, and posttraining included 1) 1 RM bench press and squat with and 2) without prestretch using free weights; 3)isokinetic peak force and power for bench press and squat at 5 degrees/s, and isotonic peak velocity and power for bench press with 20-kg load and squat with 70-kg load; 4) hydraulic peak bench press force and power, and peak knee extension torque and power at fast and slow speeds; and 5) surface anthropometry (fatfolds and girths to estimate upper arm and thigh volume and muscle area). Changes in overall fatness, muscularity, and muscle + bone cross-sectional area of the limbs did not differ between groups (P greater than 0.05). Improvements in free weight bench press and squat were similar (P greater than 0.05) in FW (approximately 24%) and HY (approximately 22%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572

Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex– or integrin alpha7–deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin

Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. DMD is characterized by a deficiency of the muscle dystrophin as a result of mutations in the dystrophin gene. Currently, no effective treatment for DMD is available. Promising molecular therapies which are mutation-specific have been developed. Transformation of an out-of-frame mRNA into an in-frame dystrophin message by inducing exon skipping is considered one of the approaches most likely to lead to success. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence results in exon skipping and production of the dystrophin protein in DMD case for the first time. After extensive studies, anti-sense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients. Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations, which are detected in 19% of DMD cases. The clinical effectiveness of gentamicin and PTC124 has been reported. We have demonstrated that arbekacin-mediated read-through can markedly ameliorate muscular dystrophy in vitro. We have already begun a clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment.

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

The aim of this study was to analyze motor unit reorganization in different types of progressive muscular dystrophies and congenital myopathies. The study population consisted of patients with genetically verified progressive muscular dystrophies: Duchenne (DMD) (n=54), Becker (BMD) (n=30), facio-scapulo-humeral (FSHD) (n=37), and Emery-Dreifuss (E-DD) (n=26). Patients with probable limb-girdle dystrophy (L-GD) (n=58) and congenital myopathies (n=35) were also included in the study. Quantitative EMG recordings were obtained from 469 muscles. Muscle activity at rest and during slight voluntary and maximal muscle contraction was analyzed. The motor unit activity potential (MUAP) duration, amplitude, area, size index (SI), polyphasicity, and the presence of "outliers" were evaluated. Diminished values of MUAP parameters and decreased maximal amplitude of maximal muscle contraction were recorded most frequently in DMD and mainly in the biceps brachii muscles. SI was the most frequently changed EMG parameter. "Outliers" with amplitude below the normal range were recorded more frequently then a decreased mean MUAP amplitude (what could indicate a very high sensitivity of this EMG parameter). Pathological interference pattern was recorded in 34.7% of biceps brachii and in 21.2% of rectus femoris muscles. In FSHD, decreased MUAP duration and SI and pathological interference pattern with low amplitude were recorded most frequently in the tibial anterior and deltoid muscles. The presence of potentials with reduced parameters is a result of decreasing motor unit area (reduced number and size of muscle fibers), while high amplitude potentials recorded in BMD and E-DD could indicate a slow and mild course of disease and muscle regeneration.

Background Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include a number of disorders with heterogeneous etiology that cause predominantly weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes. Methods PCR-sequencing analysis; sequence capture and targeted resequencing. Results Mutations of the CAPN3 gene are the most common cause of LGMD2, and mutations in this gene were identified in 71 patients in a set of 218 Czech probands with a suspicion of LGMD2. Totally, we detected 37 different mutations of which 12 have been described only in Czech LGMD2A patients. The mutation c.550delA is the most frequent among our LGMD2A probands and was detected in 47.1% of CAPN3 mutant alleles. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A (71 probands), 4.1% for LGMD2I (9 probands), 2.8% for LGMD2D (6 probands), and 1.4% for LGMD2L (3 probands). Further, we present the first results of a new approach established in the Czech Republic for diagnosis of neuromuscular diseases: sequence capture and targeted resequencing. Using this approach, we identified patients with mutations in the DYSF and SGCB genes. Conclusions We characterised a cohort of Czech LGMD2 patients on the basis of mutation analysis of genes associated with the most common forms of LGMD2 in the European population and subsequently compared the occurrence of particular forms of LGMD2 among countries on the basis of our results and published studies. PMID:25135358

Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include a number of disorders with heterogeneous etiology that cause predominantly weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes. PCR-sequencing analysis; sequence capture and targeted resequencing. Mutations of the CAPN3 gene are the most common cause of LGMD2, and mutations in this gene were identified in 71 patients in a set of 218 Czech probands with a suspicion of LGMD2. Totally, we detected 37 different mutations of which 12 have been described only in Czech LGMD2A patients. The mutation c.550delA is the most frequent among our LGMD2A probands and was detected in 47.1% of CAPN3 mutant alleles. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A (71 probands), 4.1% for LGMD2I (9 probands), 2.8% for LGMD2D (6 probands), and 1.4% for LGMD2L (3 probands).Further, we present the first results of a new approach established in the Czech Republic for diagnosis of neuromuscular diseases: sequence capture and targeted resequencing. Using this approach, we identified patients with mutations in the DYSF and SGCB genes. We characterised a cohort of Czech LGMD2 patients on the basis of mutation analysis of genes associated with the most common forms of LGMD2 in the European population and subsequently compared the occurrence of particular forms of LGMD2 among countries on the basis of our results and published studies.

The relative frequencies of different subtypes of limb-girdle muscular dystrophies vary widely among different populations. We estimated the percentage of limb-girdle muscular dystrophy subtypes in Chinese people based on 68 patients with limb-girdle muscular dystrophy from the Myology Clinic, Neurology Department, First Hospital of Jilin University, China. A diagnosis of calpainopathy was made in 12 cases (17%), and dysferlin deficiency in 10 cases (15%). Two biopsies revealed α-sarcoglycan deficiency (3%), and two others revealed a lack of caveolin-3 (3%). A diagnosis of unclassified limb-girdle muscular dystrophy was made in the remaining patients (62%). The appearances of calpain 3- and dysferlin-deficient biopsies were similar, though rimmed vacuoles were unique to dysferlinopathy, while inflammatory infiltrates were present in both these limb-girdle muscular dystrophy type 2D biopsies. Macrophages were detected in seven dysferlinopathy biopsies. The results of this study suggest that the distribution of limb-girdle muscular dystrophy subtypes in the Han Chinese population is similar to that reported in the West. The less necrotic, regenerating and inflammatory appearance of limb-girdle muscular dystrophy type 2A, but with more lobulated fibers, supports the idea that calpainopathy is a less active, but more chronic disease than dysferlinopathy. Unusual features indicated an extended limb-girdle muscular dystrophy disease spectrum. The use of acid phosphatase stain should be considered in suspected dysferlinopathies. To the best of our knowledge, this is the first report to define the relative proportions of the various forms of limb-girdle muscular dystrophy in China, based on protein testing. PMID:25206500

For health promotion and motor rehabilitation, controlling muscular fatigue on-site is important during exercise sessions. We have developed a ubiquitous wearable unit with a Linux board and tried to apply it to the control of a torque-assisted bicycle with a biosignal-based fuzzy system designed for a cycle ergometer. The results showed that an appropriate design for the cycle ergometor (indoor exercise) would be sufficiently applicable for the torque-assisted bicycle (outdoor exercise) in terms of heart rate, but was not sufficient in terms of muscular fatigue. It needs more detailed control for muscular activity.

Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mammalian target of rapamycin, serum response factor, atrogin-1, myostatin, etc.) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This review provides an overview of the adaptive changes in several regulators of muscle mass in both sarcopenia and muscular dystrophy. PMID:25221510

The use of ultrasound (US) scanning to assess the muscular function during the reinnervation is a new concept in medicine. The US signs of muscle denervation were thoroughly described in the article. The US muscle monitoring was performed by the complete and partial radial nerve injury in various follow-up periods. Absolute and relative indications for surgery were determined. The comparative characteristics of structural muscular changes, together with the US test for the assessment of the treatment efficacy and nerval and muscular recovery were suggested.

ABSTRACT Duchenne muscular dystrophy (DMD) is an recessive X-linked mediated, musculoskeletal disorder that affects only males. It is the most common and severe form of muscular dystrophy where there is failure to manufacture dystrophin. Clinically, it is characterized by progressive muscle wasting eventually leading to premature death. This case report describes the genetic, oral and systemic findings in two cases of DMD in male siblings. How to cite this article: Suneja B, Suneja ES, Adlakha VK, Chandna P. A Rare Case Report of Neurodegenerative Disease: Duchenne Muscular Dystrophy in Two Male Siblings. Int J Clin Pediatr Dent 2015;8(2):163-165. PMID:26379389

Duchenne muscular dystrophy (DMD) is a fatal, X-linked neuromuscular disease that affects 1 boy in 3500 to 5000 boys. The golden retriever muscular dystrophy dog is the best clinically relevant DMD animal model. Here, we used a high-thoughput miRNA sequencing screening for identification of candidate serum miRNA biomarkers in golden retriever muscular dystrophy dogs. We confirmed the dysregulation of the previously described muscle miRNAs, miR-1, miR-133, miR-206, and miR-378, and identified a new candidate muscle miRNA, miR-95. We identified two other classes of dysregulated serum miRNAs in muscular dystrophy: miRNAs belonging to the largest known miRNA cluster that resides in the imprinting DLK1-DIO3 genomic region and miRNAs associated with cardiac disease, including miR-208a, miR-208b, and miR-499. No simple correlation was identified between serum levels of cardiac miRNAs and cardiac functional parameters in golden retriever muscular dystrophy dogs. Finally, we confirmed a dysregulation of miR-95, miR-208a, miR-208b, miR-499, and miR-539 in a small cohort of DMD patients. Given the interspecies conservation of miRNAs and preliminary data in DMD patients, these newly identified dysregulated miRNAs are strong candidate biomarkers for DMD patients.

The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

We examine the relationships that internalization, need thwarting (NT), and drive for muscularity (DFM), along with their interactions, had with weightlifting, muscle dissatisfaction (MD), and muscle-related-worry (MRW). A sample of 552 men (MAge=20.5 years, SD=3.1) completed the Psychological Need Thwarting Scale, the Internalization subscale of the male version of the Sociocultural Attitudes Towards Appearance Questionnaire, the Drive for Muscularity Scale-Attitudes subscale, the Male Body Attitudes Scale-Muscularity subscale, the Body Change Inventory-Worry subscale, and an inventory assessing weightlifting behavior. DFM significantly predicted weightlifting, MRW, and MD. Internalization significantly predicted weightlifting and MRW. NT significantly predicted weightlifting and MD, and its relationship with MRW approached significance. The interaction terms did not predict weightlifting or MRW. The NT/DFM and NT/Internalization interaction terms predicted MD. These results highlight the role of NT in predicting appearance variables in men.

Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.

The ability of anticholinergic agents microinjected into the subthalamic nucleus to reduce reserpine-induced muscular rigidity was assessed in rats. The electromyographical activity of the gastrocnemius-soleus muscle was used as a parameter of muscular rigidity. Reserpine (5 mg/kg i.p.) produced the appearance of electromyographical activity. The muscarinic antagonists M3 (1.27 nmol of 4-DAMP) and M1 (2.36 nmol of pirenzepine) markedly reduced the reserpine-induced electromyographical activity, whereas the M2 antagonist AFDX-116 (2.37 nmol) had no effect. These results suggest that a high cholinergic tone in the subthalamic nucleus is associated with the reserpine-induced muscular rigidity. Moreover, the M3 muscarinic antagonist is more effective than the M1 muscarinic antagonist in reducing the muscular rigidity in reserpinized rats, a model of Parkinson's disease, by blocking the high cholinergic tone in the subthalamic nucleus.

Hereditary spinal muscular atrophy is a motor neuron disorder characterized by muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord. Initially, the disease was considered purely as an autosomal recessive condition caused by loss-of-function SMN1 mutations on 5q13. Recent developments in next generation sequencing technologies, however, have unveiled a growing number of clinical conditions designated as non-5q forms of spinal muscular atrophy. At present, 16 different genes and one unresolved locus are associated with proximal non-5q forms, having high phenotypic variability and diverse inheritance patterns. This review provides an overview of the current knowledge regarding the phenotypes, causative genes, and disease mechanisms associated with proximal SMN1-negative spinal muscular atrophies. We describe the molecular and cellular functions enriched among causative genes, and discuss the challenges in the post-genomics era of spinal muscular atrophy research. PMID:24970098

The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial.

Presently, objectification theory has yielded mixed results when utilized to explain body image concerns in men. An online survey assessing internalization of media ideals, self-objectification, body surveillance, body shame, the drive for muscularity, and body mass index (BMI) was completed by 244 predominantly college-aged males. Path analyses were used to investigate relationships among these variables where it was hypothesized that objectification variables would mediate the relationship between internalization of media ideals and the drive for muscularity. Internalization of media ideals was the strongest predictor of the drive for muscularity, followed by BMI, though variables of objectification theory had no impact on the drive for muscularity contrary to hypotheses. The results suggest that objectification theory may not be applicable to men as it is currently measured.

Muscular strength is a well-known predictor of morbidity and mortality. Similarly, self-esteem is a predictor of health and well-being. The relationship between these two variables, however, is currently unknown. This study examined the cross-sectional relationship between maximal muscular strength (i.e. handgrip and one-repetition-maximum (1-RM) squat) and global self-esteem in 126 college students. Significant correlations were found between both measures of muscular strength and self-esteem. Further analyses revealed that these relationships were only significant for men. Based on these results, additional research is needed to further explore the relationship between muscular strength and self-esteem, especially in other demographic groups and longitudinally.

This study examined the role of positive and negative appearance-based comments on body dissatisfaction and drive for muscularity among young adult males. The direct and moderating effect of self-esteem were also investigated; and BMI, age, and social desirability were included as covariates. The participants were 214 males aged between 18 and 30 years. More frequent negative comments were associated with higher body dissatisfaction whilst more frequent positive comments were associated with lower body dissatisfaction. However, both frequent negative and positive commentary were associated with higher drive for muscularity. Self-esteem was also associated with both body dissatisfaction and the drive for muscularity, but it did not moderate that influence of either positive or negative messages. Longitudinal research is now needed to determine the directionality of these relationships. Further research is required to establish the contexts in which positive and negative messages are associated with body dissatisfaction and the drive for muscularity.

A substantial body of research documents that exposure to images depicting a "thin ideal" body figure effects women's state-oriented body satisfaction. However, there is evidence that the societal ideal body figure of females is evolving to be not just thin, but also muscular or toned. Therefore, the purpose of this research was to test the effect of exposure to ideal body figures that are both thin and muscular on female state body satisfaction. Researchers recruited female participants (N=366) from an online community (Amazon's Mechanical Turk) and randomly assigned them to view images in one of four conditions: thin, thin and muscular, thin and hypermuscular, and control (images of cars). Results indicated that state-oriented body satisfaction decreased in the thin condition and thin and muscular condition, but not the hypermuscular or control conditions. These findings have implications for clinical initiatives as well as future research.

The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep. PMID:26474044